The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A class of enzymes that catalyzes the ATP-dependent formation of a thioester bond between itself and UBIQUITIN. It then transfers the activated ubiquitin to one of the UBIQUITIN-PROTEIN LIGASES.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
A phosphatidylinositol 3-kinase subclass that includes enzymes whose specificity is limited to 1-phosphatidylinositol. Members of this class play a role in vesicular transport and in the regulation of TOR KINASES.
Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. Loss of expression of lysosomal-associated membrane protein 2 is associated with GLYCOGEN STORAGE DISEASE TYPE IIB.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Proteolytic breakdown of the MITOCHONDRIA.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Macromolecular complexes formed from the association of defined protein subunits.
The process by which chemical compounds provide protection to cells against harmful agents.
Lengthy and continuous deprivation of food. (Stedman, 25th ed)
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
Established cell cultures that have the potential to propagate indefinitely.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)
The chemical reactions involved in the production and utilization of various forms of energy in cells.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)

LB-AUT7, a novel symbiosis-regulated gene from an ectomycorrhizal fungus, Laccaria bicolor, is functionally related to vesicular transport and autophagocytosis. (1/5833)

We have identified LB-AUT7, a gene differentially expressed 6 h after ectomycorrhizal interaction between Laccaria bicolor and Pinus resinosa. LB-Aut7p can functionally complement its Saccharomyces cerevisiae homolog, which is involved in the attachment of autophagosomes to microtubules. Our findings suggest the induction of an autophagocytosis-like vesicular transport process during ectomycorrhizal interaction.  (+info)

Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways. (2/5833)

Proper functioning of organelles necessitates efficient protein targeting to the appropriate subcellular locations. For example, degradation in the fungal vacuole relies on an array of targeting mechanisms for both resident hydrolases and their substrates. The particular processes that are used vary depending on the available nutrients. Under starvation conditions, macroautophagy is the primary method by which bulk cytosol is sequestered into autophagic vesicles (autophagosomes) destined for this organelle. Molecular genetic, morphological, and biochemical evidence indicates that macroautophagy shares much of the same cellular machinery as a biosynthetic pathway for the delivery of the vacuolar hydrolase, aminopeptidase I, via the cytoplasm-to-vacuole targeting (Cvt) pathway. The machinery required in both pathways includes a novel protein modification system involving the conjugation of two autophagy proteins, Apg12p and Apg5p. The conjugation reaction was demonstrated to be dependent on Apg7p, which shares homology with the E1 family of ubiquitin-activating enzymes. In this study, we demonstrate that Apg7p functions at the sequestration step in the formation of Cvt vesicles and autophagosomes. The subcellular localization of Apg7p fused to green fluorescent protein (GFP) indicates that a subpopulation of Apg7pGFP becomes membrane associated in an Apg12p-dependent manner. Subcellular fractionation experiments also indicate that a portion of the Apg7p pool is pelletable under starvation conditions. Finally, we demonstrate that the Pichia pastoris homologue Gsa7p that is required for peroxisome degradation is functionally similar to Apg7p, indicating that this novel conjugation system may represent a general nonclassical targeting mechanism that is conserved across species.  (+info)

Glucose-induced autophagy of peroxisomes in Pichia pastoris requires a unique E1-like protein. (3/5833)

Cytosolic and peroxisomal enzymes necessary for methanol assimilation are synthesized when Pichia pastoris is grown in methanol. Upon adaptation from methanol to a glucose environment, these enzymes are rapidly and selectively sequestered and degraded within the yeast vacuole. Sequestration begins when the vacuole changes shape and surrounds the peroxisomes. The opposing membranes then fuse, engulfing the peroxisome. In this study, we have characterized a mutant cell line (glucose-induced selective autophagy), gsa7, which is defective in glucose-induced selective autophagy of peroxisomes, and have identified the GSA7 gene. Upon glucose adaptation, gsa7 cells were unable to degrade peroxisomal alcohol oxidase. We observed that the peroxisomes were surrounded by the vacuole, but complete uptake into the vacuole did not occur. Therefore, we propose that GSA7 is not required for initiation of autophagy but is required for bringing the opposing vacuolar membranes together for homotypic fusion, thereby completing peroxisome sequestration. By sequencing the genomic DNA fragment that complemented the gsa7 phenotype, we have found that GSA7 encodes a protein of 71 kDa (Gsa7p) with limited sequence homology to a family of ubiquitin-activating enzymes, E1. The knockout mutant gsa7Delta had an identical phenotype to gsa7, and both mutants were rescued by an epitope-tagged Gsa7p (Gsa7-hemagglutinin [HA]). In addition, a GSA7 homolog, APG7, a protein required for autophagy in Saccharomyces cerevisiae, was capable of rescuing gsa7. We have sequenced the human homolog of GSA7 and have shown many regions of identity between the yeast and human proteins. Two of these regions align to the putative ATP-binding domain and catalytic site of the family of ubiquitin activating enzymes, E1 (UBA1, UBA2, and UBA3). When either of these sites was mutated, the resulting mutants [Gsa7(DeltaATP)-HA and Gsa7(C518S)-HA] were unable to rescue gsa7 cells. We provide evidence to suggest that Gsa7-HA formed a thio-ester linkage with a 25-30 kDa protein. This conjugate was not observed in cells expressing Gsa7(DeltaATP)-HA or in cells expressing Gsa7(C518S)-HA. Our results suggest that this unique E1-like enzyme is required for homotypic membrane fusion, a late event in the sequestration of peroxisomes by the vacuole.  (+info)

Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy. (4/5833)

In the yeast Saccharomyces cerevisiae, the Apg12p-Apg5p conjugating system is essential for autophagy. Apg7p is required for the conjugation reaction, because Apg12p is unable to form a conjugate with Apg5p in the apg7/cvt2 mutant. Apg7p shows a significant similarity to a ubiquitin-activating enzyme, Uba1p. In this article, we investigated the function of Apg7p as an Apg12p-activating enzyme. Hemagglutinin-tagged Apg12p was coimmunoprecipitated with c-myc-tagged Apg7p. A two-hybrid experiment confirmed the interaction. The coimmunoprecipitation was sensitive to a thiol-reducing reagent. Furthermore, a thioester conjugate of Apg7p was detected in a lysate of cells overexpressing both Apg7p and Apg12p. These results indicated that Apg12p interacts with Apg7p via a thioester bond. Mutational analyses of Apg7p suggested that Cys507 of Apg7p is an active site cysteine and that both the ATP-binding domain and the cysteine residue are essential for the conjugation of Apg7p with Apg12p to form the Apg12p-Apg5p conjugate. Cells expressing mutant Apg7ps, Apg7pG333A, or Apg7pC507A showed defects in autophagy and cytoplasm-to-vacuole targeting of aminopeptidase I. These results indicated that Apg7p functions as a novel protein-activating enzyme necessary for Apg12p-Apg5p conjugation.  (+info)

A 60 kDa plasma membrane protein changes its localization to autophagosome and autolysosome membranes during induction of autophagy in rat hepatoma cell line, H-4-II-E cells. (5/5833)

We previously reported the preparation and characterization of an antibody against membrane fraction of autolysosomes from rat liver (J. Histochem. Cytochem. 38, 1571-1581, 1990). Immunoblot analyses of total membrane fraction of a rat hepatoma cell line, H-4-II-E cells by this antibody suggested that H-4-II-E cells expressed several autolysosomal proteins, including a protein with apparent molecular weight of 60 kDa. It was suggested that this 60 kDa protein was a peripheral membrane protein, because it was eluted from the membrane by sodium carbonate treatment. We prepared an antibody against this 60 kDa protein by affinity purification method, and examined its behavior during induction of autophagy. Autophagy was induced by transferring the cells from Dulbecco's modified Eagle medium (DMEM) containing 12% fetal calf serum into Hanks' balance salt solution. In DMEM, the 60 kDa protein showed diffused immunofluorescence pattern, and immunoelectron microscopy suggested that this protein was located on the extracellular side of the plasma membrane. After inducing autophagy, the immunofluorescence configuration of the 60 kDa protein changed from the diffused pattern to a granulous one. Immunoelectron microscopy showed that the 60 kDa protein was localized on the luminal side of the limiting membrane of autolysosomes and endosomes. In the presence of bafilomycin A1 which prevents fusion between autophagosomes and lysosomes, the 60 kDa protein was localized on the limiting membrane of the autophagosomes and endosomes. These results suggest that the 60 kDa protein is transported from the plasma membrane to the autophagosome membrane through the endosomes.  (+info)

A human intracellular apyrase-like protein, LALP70, localizes to lysosomal/autophagic vacuoles. (6/5833)

Using antibodies against autophagic vacuole membrane proteins we identified a human cDNA with an open reading frame of 1848 bp, encoding a protein of 70 kDa, which we named lysosomal apyrase-like protein of 70 kDa (LALP70). Sequence analysis revealed that LALP70 belongs to the apyrase or GDA1/CD39 family and is almost identical to a human uridine diphosphatase, with the exception of nine extra amino acids in LALP70. Members of this family were originally described as ectoenzymes, with some intracellular exceptions. Transfected LALP70 fused to the green fluorescent protein localized in the cytoplasm with a punctate pattern in the perinuclear space. These structures colocalized with the autophagic marker monodansylcadaverine and the lysosomal protein lamp1. Hydrophobicity analysis of the encoded protein revealed a transmembrane region at the N and C termini. Most of the sequence is arranged between these transmembrane domains, and contains four apyrase conserved regions. In vitro transcription/translation in the presence of microsomes showed that no signal sequence is cleaved off and that the translation product is protected from trypsin treatment. Our data indicate that LALP70 is a type III lysosomal/autophagic vacuole membrane protein with the apyrase conserved regions facing the luminal space of the vacuoles.  (+info)

Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. (7/5833)

Autophagy is an intracellular bulk degradation system that is ubiquitous for eukaryotic cells. In this process, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. We recently found that a protein conjugation system, in which Apg12p is covalently attached to Apg5p, is indispensable for autophagy in yeast. Here, we describe a novel coiled-coil protein, Apg16p, essential for autophagy. Apg16p interacts with Apg12p-conjugated Apg5p and less preferentially with unconjugated Apg5p. Moreover, the coiled-coil domain of Apg16p mediates self-multimerization that leads to cross-linking of Apg5p molecules and formation of a stable protein complex. Apg16p is not essential for the Apg12p-Apg5p conjugation reaction. These results suggest that the Apg12p-Apg5p conjugate requires Apg16p to accomplish its role in the autophagy pathway, and Apg16p is a key molecule as a linker to form the Apg12p-Apg5p-Apg16p multimer.  (+info)

Clathrin functions in the absence of heterotetrameric adaptors and AP180-related proteins in yeast. (8/5833)

The major coat proteins of clathrin-coated vesicles are the clathrin triskelion and heterotetrameric associated protein (AP) complexes. The APs are thought to be involved in cargo capture and recruitment of clathrin to the membrane during endocytosis and sorting in the trans-Golgi network/endosomal system. AP180 is an abundant coat protein in brain clathrin-coated vesicles, and it has potent clathrin assembly activity. In Saccharomyces cerevisiae, there are 13 genes encoding homologs of heterotetrameric AP subunits and two genes encoding AP180-related proteins. To test the model that clathrin function is dependent on the heterotetrameric APs and/or AP180 homologs, yeast strains containing multiple disruptions in AP subunit genes, as well as in the two YAP180 genes, were constructed. Surprisingly, the AP deletion strains did not display the phenotypes associated with clathrin deficiency, including slowed growth and endocytosis, defective late Golgi protein retention and impaired cytosol to vacuole/autophagy function. Clathrin-coated vesicles isolated from multiple AP deletion mutants were morphologically indistinguishable from those from wild-type cells. These results indicate that clathrin function and recruitment onto membranes are not dependent upon heterotetrameric adaptors or AP180 homologs in yeast. Therefore, alternative mechanisms for clathrin assembly and coated vesicle formation, as well as the role of AP complexes and AP180-related proteins in these processes, must be considered.  (+info)

We compared the effect of short- and long-established steatosis on the intensity of autophagy-lysosomal pathway in rat liver A commonly used approach to monitor and analyze autophagy flux is via blockade of autophagic activity. Thus, decreasing autophagy appears to prevent neuronal degeneration The LC3 Antibody Kit for Autophagy includes a rabbit polyclonal antibody against LC3B that has been validated for use in fluorescence microscopy and high content imaging and analysis. 2012) while Bafilomycin A1 and chloroquine inhibit the autophagy by neutralizing the lysosomal pH and blocking autophagosome-lysosome fusion (see Fig. …. Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. An advantage to monitoring p62 to measure autophagic flux is that lysosomal inhibitors are not necessary, because unlike LC3-II, p62 does not usually increase when autophagy is induced. 2 and then switched to MAS buffer before permeabilization with PMP and ...
Herein, we implicate for the first time the REDD1/autophagy pathway in neutrophil-mediated end-organ injury in SLE. Serum from patients with active SLE-a surrogate of the inflammatory microenvironment in SLE-through ET-1 and HIF-1α, upregulates neutrophil REDD1 expression, resulting in autophagy induction and subsequent NET release. Bioactive IL-17A- and TF-decorated NETs, detected in active lupus kidney and skin, activate tissue resident cells mediating inflammation and fibrosis.. Autophagy is enhanced in lupus T cells44 and B cells.45 Herein, to elucidate the mechanism underlying NET release in SLE, we investigated autophagy in SLE neutrophils and its association to NET release. We demonstrate that active SLE neutrophils display increased basal autophagy levels mediated by inflammatory mediators within active SLE sera. We link NETs with autophagy in SLE and provide evidence that HCQ, a late-stage autophagy inhibitor, has a key role in NETs reduction through autophagy inhibition. Our data ...
Autophagy is a conserved process that delivers components of the cytoplasm to lysosomes for degradation. The E1 and E2 enzymes encoded by Atg7 and Atg3 are thought to be essential for autophagy involving the ubiquitin-like protein Atg8. Here, we describe an Atg7- and Atg3-independent autophagy pathway that facilitates programmed reduction of cell size during intestine cell death. Although multiple components of the core autophagy pathways, including Atg8, are required for autophagy and cells to shrink in the midgut of the intestine, loss of either Atg7 or Atg3 function does not influence these cellular processes. Rather, Uba1, the E1 enzyme used in ubiquitylation, is required for autophagy and reduction of cell size. Our data reveal that distinct autophagy programs are used by different cells within an animal, and disclose an unappreciated role for ubiquitin activation in autophagy.
Autophagy is a critical process for recycling of cytoplasmic materials during environmental stress, senescence and cellular remodeling. It is upregulated under a wide range of abiotic stress conditions and is important for stress tolerance. Autophagy is repressed by the protein kinase target of rapamycin (TOR), which is activated in response to nutrients and in turn upregulates cell growth and translation and inhibits autophagy. Down-regulation of TOR in Arabidopsis thaliana leads to constitutive autophagy and to decreased growth, but the relationship to stress conditions is unclear. Here, we assess the extent to which TOR controls autophagy activation by abiotic stress. Overexpression of TOR inhibited autophagy activation by nutrient starvation, salt and osmotic stress, indicating that activation of autophagy under these conditions requires down-regulation of TOR activity. In contrast, TOR overexpression had no effect on autophagy induced by oxidative stress or ER stress, suggesting that activation of
Full Text - Autophagy, a highly conserved cellular proteolysis process, has been involved in non-small cell lung cancer (NSCLC). We tried to develop a prognostic prediction model for NSCLC patients based on the expression profiles of autophagy-associated genes. Univariate Cox regression analysis was used to determine autophagy-associated genes significantly correlated with overall survival (OS) of the TCGA lung cancer cohort. LASSO regression was performed to build multiple-gene prognostic signatures. We found that the 22-gene and 11-gene signatures could dichotomize patients with significantly different OS and independently predict the OS in TCGA lung adenocarcinoma (HR=2.801, 95% CI=2.252-3.486, P<0.001) and squamous cell carcinoma (HR=1.105, 95% CI=1.067-1.145, P<0.001), respectively. The prognostic performance of the 22-gene signature was validated in four GEO lung cancer cohorts. Moreover, GO, KEGG, and GSEA analyses unveiled several fundamental signaling pathways and cellular
Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Recently, matrine has been reported to induce autophagy and autophagic cell death in cancer cells, although the underlying mechanisms have yet to be elucidated. Here, we systematically examined the autophagic events induced by matrine in SGC7901 cells. The accumulation of autophagic vacuoles in matrine-treated cells was verified by the conversion of microtubule-associated protein light chain 3 as well as confocal and transmission electron microscopy. Furthermore, we demonstrated that matrine blocked autophagic degradation by ...
Before Its News). Publishers, Autophagy modulators-Pipeline Insights, 2017″, report provides in depth insights on the pipeline drugs and their development activities around the Autophagy modulators. The Publishers Report covers the product profiles in various stages of development including Discovery, Pre-clinical, IND, Phase I, Phase II, Phase III and Preregistration. Report covers the product clinical trials information and other development activities including technology, licensing, collaborations, acquisitions, fundings, patent and USFDA & EMA designations details. Publishers Report also provides detailed information on the discontinued and dormant drugs that have gone inactive over the years for Autophagy modulators. Publishers Report also assesses the Autophagy modulators therapeutics by Monotherapy, Combination products, Molecule type and Route of Administration.. For more information at http://www.reportsweb.com/autophagy-modulators-pipeline-insights-2017 .. Report Scope. - The ...
Reactive oxygen species (ROS) have been commonly accepted as inducers of autophagy, and autophagy in turn is activated to relieve oxidative stress. Yet, whether and how oxidative stress, generated in various human pathologies, regulates autophagy remains unknown. Here, we mechanistically studied the role of TRPM2 (transient receptor potential cation channel subfamily M member 2)-mediated Ca2+ influx in oxidative stress-mediated autophagy regulation. On the one hand, we demonstrated that oxidative stress triggered TRPM2-dependent Ca2+ influx to inhibit the induction of early autophagy, which renders cells more susceptible to death. On the other hand, oxidative stress induced autophagy (and not cell death) in the absence of the TRPM2-mediated Ca2+ influx. Moreover, in response to oxidative stress, TRPM2-mediated Ca2+ influx activated CAMK2 (calcium/calmodulin dependent protein kinase II) at levels of both phosphorylation and oxidation, and the activated CAMK2 subsequently phosphorylated ...
A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4(+) T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3(+) Treg cells. Specific ablation of Atg16l1 in Foxp3(+) Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic
TY - JOUR. T1 - Autophagy-mediated stress response in motor neuron after transient ischemia in rabbits. AU - Baba, Hironori. AU - Sakurai, Masahiro. AU - Abe, Koji. AU - Tominaga, Ryuji. PY - 2009/8. Y1 - 2009/8. N2 - Objective: Spinal cord injury is considered to be related to a vulnerability of spinal motor neurons to ischemia. However, the mechanisms underlying this vulnerability are not fully understood. We investigated the role of autophagy, which is an intracellular bulk degradation process, at motor neuron as a potential mechanism of neuronal death by immunohistochemical analysis for microtubule-associated protein light chain3 (LC3) and γ-aminobutyric-acid type-A-receptor-associated protein (GABARAP) which are considered as markers of autophagy. Methods: We used a rabbit spinal cord ischemia model with the use of a balloon catheter. The spinal cord was removed at 8 hours, 1, 2, or 7 days after 15 minutes of transient ischemia, and histologic changes were examined with hematoxylin-eosin ...
Autophagy is the major intracellular system which is critical for the removal of harmful protein aggregates and malfunctioning organelles. Dysfunctional autophagy is associated with a multitude of human diseases, such as protein aggregation in Alzheimers disease and non-successful aging. Major interest exists in the dietary manipulation of the autophagy pathway activity, so as to tune the cells protein degradation capabilities and to prevent cell death onset. It has recently become clear that the machinery required to degrade protein cargo has a distinct activity level which can be altered through specific dietary modulation. Moreover, this activity may differ from that of the proteinaceous cargo. Overall, brain health and successful aging are characterized by limited protein aggregation, with a distinct molecular signature of maintained autophagy function. However, it is largely unclear how to control autophagy through dietary interventions with a precision that would allow to maintain minimal levels
Autophagy is a process of cellular self-degradation and is a major pathway for elimination of cytoplasmic material by the lysosomes. Autophagy is responsible for the degradation of damaged organelles and protein aggregates and therefore plays a significant role in cellular homeostasis. Despite the initial belief that autophagy is a nonselective bulk process, there is growing evidence during the last years that sequestration and degradation of cellular material by autophagy can be accomplished in a selective and specific manner. Given the role of autophagy and selective autophagy in several disease related processes such as tumorigenesis, neurodegeneration and infections, it is very important to dissect the molecular mechanisms of selective autophagy, in the context of the system and the organism. An excellent genetically tractable model organism to study autophagy is Drosophila, which appears to have a highly conserved autophagic machinery compared with mammals. However, the mechanisms of selective
Autophagy plays an essential role in cell survival/death and functioning. Modulation of autophagy has been recognized as a promising therapeutic strategy against diseases/disorders associated with uncontrolled growth or accumulation of biomolecular aggregates, organelles or cells including those caused by cancer, aging, neurodegeneration, and liver diseases such as α1-antitrypsin deficiency. Numerous pharmacological agents that enhance or suppress autophagy have been discovered. However, their molecular mechanisms of action are far from clear. Here we collected a set of 225 autophagy modulators and carried out a comprehensive quantitative systems pharmacology (QSP) analysis of their targets using both existing databases and predictions made by our machine learning algorithm. Autophagy modulators include several highly promiscuous drugs (e.g. artenimol and olanzapine acting as activator, fostamatinib as inhibitor, or melatonin as dual-modulator), as well as selected drugs uniquely targeting specific
Autophagy is a conserved constitutive cellular process, responsible for the degradation of dysfunctional proteins and organelles. Autophagy plays a role in many diseases such as neurodegeneration and cancer; however, to date, conventional autophagy detection techniques are not suitable for clinical samples. We have developed a high throughput, statistically robust technique that quantitates autophagy in primary human leukocytes using the Image stream, an imaging flow cytometer. We validate this method on cell lines and primary cells knocked down for essential autophagy genes. Also, using this method we show that T cells have higher autophagic activity than B cells. Furthermore our results indicate that healthy primary senescent CD8(+) T cells have decreased autophagic levels correlating with increased DNA damage, which may explain features of the senescent immune system and its declining function with age. This technique will allow us, for the first time, to measure autophagy levels in diseases with a
Background: Autophagy is a biological process that cells engulf their cytoplasmic proteins or organelles to achieve the needs of metabolic and renewal. microRNAs can affect the development of cancer by regulating cell autophagy. We aim to identify the autophagy-associated Micr...
A variety of mechanisms deliver cytosolic materials to the lysosomal compartment for degradation through autophagy. Here, we focus on two autophagic pathways, the chaperone-mediated autophagy and the endosomal microautophagy that rely on the cytosolic chaperone hsc70 for substrate targeting. Although hsc70 participates in the triage of proteins for degradation by different proteolytic systems, the common characteristic shared by these two forms of autophagy is that hsc70 binds directly to a specific five-amino acid motif in the cargo protein for its autophagic targeting. We summarize the current understanding of the molecular machineries behind each of these types of autophagy.. ...
Autophagy is an intracellular process responsible for the degradation and recycling of cytoplasmic components. It selectively removes harmful cellular material and enables the cell to survive starvation by mobilizing nutrients via the bulk degradation of cytoplasmic components. While research over the last decades has led to the discovery of the key factors involved in autophagy, the pathway is not yet completely understood. The first studies of autophagy on a molecular level were conducted in the yeast Saccharomyces cerevisiae. Building up on these studies, many homologs have been found in higher eukaryotes. Yeast remains a highly relevant model organism for studying autophagy, with a wide range of established methods to elucidate the molecular details of the autophagy pathway. In this review, we provide an overview of methods to study both selective and bulk autophagy, including intermediate steps in the yeast Saccharomyces cerevisiae. We compare different assays, discuss their advantages and
The regulated lysosomal degradation pathway of autophagy prevents cellular damage and thus protects from malignant transformation. Autophagy is also required for the maturation of various hematopoietic lineages, namely the erythroid and lymphoid ones, yet its role in adult hematopoietic stem cells (HSCs) remained unexplored. While normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs or early progenitors leads to leukemia. Mechanisms protecting HSCs from cellular damage are therefore essential to prevent hematopoietic malignancies. By conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system, we found that autophagy is required for the maintenance of true HSCs and therefore also of downstream hematopoietic progenitors. Loss of autophagy in HSCs leads to the expansion of a progenitor cell population in the bone marrow, giving rise to a severe, invasive myeloproliferation, which strongly resembles human acute myeloid leukemia (AML).
Mitochondrial autophagy is an important adaptive stress response and can be modulated by various key molecules. A previous study found that the regulator of calcineurin 1-1L (Rcan1-1L) may regulate mitochondrial autophagy and cause mitochondria degradation in neurocytes. However, the effect of Rcan1-1L on cardiomyocytes has not been determined. In the present study, we aimed to investigate the role of Rcan1-1L in angiotensin II (Ang II)-exposed human cardiomyocytes. Above all, Human adult cardiac myocytes (HACMs) were exposed to 200 nmol/L Ang II for 4 days. Enhanced H{sub 2}O{sub 2} production, cytochrome C release and mitochondrial permeability were observed in these cells, which were blocked by valsartan. Consistently, Ang II exposure significantly reduced cardiomyocyte viability. However, transfection of Rcan1-1L vector promoted cell viability and ameliorated the apoptosis caused by Ang II. Rcan1-1L clearly promoted mitochondrial autophagy in HACMs, with elevated autophagy protein (ATG) 5 ...
Autophagy can be an conserved membrane trafficking procedure evolutionarily. phosphoinositide 3-kinases (PI3Ks) dissociates from development element receptor complexes and raises its discussion with the tiny GTPase Rab5. This p110β-Rab5 association maintains Rab5 in its GTP-bound condition and enhances the Rab5-Vps34 discussion that promotes autophagy. p110β mutants that neglect to connect to Rab5 are faulty in autophagy advertising. Therefore in mammalian cells p110β works as a molecular sensor for development SRT3109 element availability and induces autophagy by activating a Rab5-mediated SRT3109 signaling cascade. Intro Autophagy can be a membrane trafficking procedure that delivers intracellular material destined for degradation right into a dual membrane framework termed an autophagosome that after that fuses using the lysosome (Levine and Kroemer 2008 Levine and Yuan 2005 Mizushima et al. 2008 In metazoans the initiation of autophagy can be critically controlled by several phospholipids ...
Macroautophagy/autophagy is the main intracellular catabolic pathway in neurons that eliminates misfolded proteins, aggregates and damaged organelles associated with ageing and neurodegeneration. Autophagy is regulated by both MTOR-dependent and -independent pathways. There is increasing evidence that autophagy is compromised in neurodegenerative disorders, which may contribute to cytoplasmic sequestration of aggregation-prone and toxic proteins in neurons. Genetic or pharmacological modulation of autophagy to promote clearance of misfolded proteins may be a promising therapeutic avenue for these disorders. Here, we demonstrate robust autophagy induction in motor neuronal cells expressing SOD1 or TARDBP/TDP-43 mutants linked to amyotrophic lateral sclerosis (ALS). Treatment of these cells with rilmenidine, an anti-hypertensive agent and imidazoline-1 receptor agonist that induces autophagy, promoted autophagic clearance of mutant SOD1 and efficient mitophagy. Rilmenidine administration to mutant ...
TY - JOUR. T1 - Diindolylmethane and its halogenated derivatives induce protective autophagy in human prostate cancer cells via induction of the oncogenic protein AEG-1 and activation of AMP-activated protein kinase (AMPK). AU - Draz, Hossam. AU - Goldberg, Alexander A.. AU - Titorenko, Vladimir I.. AU - Tomlinson Guns, Emma S.. AU - Safe, Stephen H.. AU - Sanderson, J. Thomas. PY - 2017/12. Y1 - 2017/12. N2 - 3,3′-Diindolylmethane (DIM) and its synthetic halogenated derivatives 4,4′-Br2- and 7,7′-Cl2DIM (ring-DIMs) have recently been shown to induce protective autophagy in human prostate cancer cells. The mechanisms by which DIM and ring-DIMs induce autophagy have not been elucidated. As DIM is a mitochondrial ATP-synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of intracellular AMP/ATP ratios and activation of AMP-activated protein kinase (AMPK) signaling in prostate cancer cells. We found that DIM and ring-DIMs induced autophagy was accompanied ...
The present study confirms the cytoprotective role of autophagy during. When autophagy was induced by rapamycin, the JAK2/STAT3 pathway was activated and VEGFA was elevated, which was attenuated after deactivating STAT3 by S3I-201. To confirm that the sensitizing effect of NAC1 inhibition on the cytotoxicity of cisplatin was attributed to suppression of autophagy, we assessed the effects of the autophagy inhibitors 3-methyladenosine and chloroquine, and small interfering RNAs (siRNAs) targeting …. Autophagy inhibitors, such as chloroquine and hydroxychloroquine, have already been clinically approved, promoting drug combination treatment by targeting autophagic pathways as a means of chloroquine and autophagy inhibitor discovering and developing more novel and more effective cancer therapeutic approaches.. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for. Abstract. The aim of this study was to explore the mechanisms of ...
Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target
Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl/LC3 co-localization in both ...
Autophagy is an evolutionarily conserved intracellular process that is used for delivering proteins and organelles to the lysosome for degradation. For decades, autophagy has been speculated to regulate amyloid-β peptide (Aβ) accumulation, which is involved in Alzheimers disease (AD); however, specific autophagic effects on the Aβ kinetics only have begun to be explored. We develop a mathematical model for autophagy with respect to Aβ kinetics and perform simulations to understand the quantitative relationship between Aβ levels and autophagy activity. In the case of an abnormal increase in the Aβ generation, the degradation, secretion, and clearance rates of Aβ are significantly changed, leading to increased levels of Aβ. When the autophagic Aβ degradation is defective in addition to the increased Aβ generation, the Aβ-regulation failure is accompanied by elevated concentrations of autophagosome and autolysosome, which may further clog neurons. The model predicts that modulations of
Neuroblastoma is an extracranial solid tumor that mainly occurs in children. It is derived from embryonic neural crest cells of the peripheral sympathetic nervous system. The overall survival rate of malignant neuroblastoma patients is very poor despite multi-modal therapy including surgery, radiotherapy, and chemotherapy. Efficacy of chemotherapy is often compromised due to presence of autophagy, which is a survival mechanism in solid tumors. Autophagy is a catablolic process for lysosomal degradation of cytoplasmic contents for recycling and it is activated during stress such as nutrient starvation and growth factor deprivation. The hallmark of autophagy is generation of double membrane structure called autophagosome that contains the microtubule-associated protein light chain 3 form II (LC3 II). In this study, we used rapamycin to mimic starvation-induced autophagy in human malignant neuroblastoma SK-N-BE2 and IMR32 cells and then investigated capability of the combination of LC3 II knockdown ...
The autophagic pathway participates in many physiological and pathophysiological processes. Autophagy plays an important role, as part of the innate immune response, in the first line of defense against intruding pathogens. Recognition of pathogens by the autophagic machinery is mainly mediated by autophagic adaptors, proteins that simultaneously interact with specific cargos and components of the autophagic machinery. However, the exact mechanisms and signaling pathways regulating this step are largely unknown. TANK-binding kinase 1 (TBK1) has been recently implicated in the autophagic clearance of the bacterium Salmonella enterica. After its activation by the invading bacteria, TBK1 directly phosphorylated the autophagic adaptor optineurin (OPTN). This modification led to enhanced interaction of OPTN with the family of mammalian Atg8 proteins, which are ubiquitin-like and essential for autophagy. Such interaction allows the autophagic machinery to be recruited to the intracellular loci of the ...
Autophagy is a constitutive lysosomal catabolic pathway that degrades damaged organelles and protein aggregates. Stem cells are characterized by self-renewal, pluripotency, and quiescence; their long life span, limited capacity to dilute cellular waste and spent organelles due to quiescence, along with their requirement for remodeling in order to differentiate, all suggest that they require autophagy more than other cell types. Here, we review the current literature on the role of autophagy in embryonic and adult stem cells, including hematopoietic, mesenchymal, and neuronal stem cells, highlighting the diverse and contrasting roles autophagy plays in their biology. Furthermore, we review the few studies on stem cells, lysosomal activity, and autophagy. Novel techniques to detect autophagy in primary cells are required to study autophagy in different stem cell types. These will help to elucidate the importance of autophagy in stem cells during transplantation, a promising therapeutic approach for many
Oxidative stress is an important pathogenic factor in influenza A virus infection. It has been found that reactive oxygen species induced by the H9N2 influenza virus is associated with viral replication. However, the mechanisms involved remain to be elucidated. In this study, the role of autophagy was investigated in H9N2 influenza virus-induced oxidative stress and viral replication in A549 cells. Autophagy induced by H9N2 was inhibited by an autophagy inhibitor or RNA interference, the autophagy level, viral replication and the presence of oxidative stress were detected by western blot, TCID50 assay, and Real-time PCR. Then autophagy and oxidative stress were regulated, and viral replication was determined. At last, the Akt/TSC2/mTOR signaling pathways was detected by western blot. Autophagy was induced by the H9N2 influenza virus and the inhibition of autophagy reduced the viral titer and the expression of nucleoprotein and matrix protein. The blockage of autophagy suppressed the H9N2 virus-induced
Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells Ji-Fan Lin,1 Yi-Chia Lin,2 Te-Fu Tsai,2,3 Hung-En Chen,2 Kuang-Yu Chou,2,3 Thomas I-Sheng Hwang2–4 1Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 2Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, 3Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, 4Department of Urology, Taipei Medical University, Taipei, Taiwan Purpose: Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC
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Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans.. ...
Hashimotos thyroiditis (HT) represents the most common organ-specific autoimmune disease. Inflammatory factors and Reactive Oxygen Species (ROS) play detrimental roles during the pathogenesis of HT. In this study, we found that thyroid follicular cells (TFCs) from HT patients expressed an elevated level of interleukin-23 (IL-23), which contributed to autophagy suppression and ROS accumulation. Additionally, IL-23-induced autophagy suppression and ROS accumulation in human TFCs was attributed to AKT/mTOR/NF-κB signalling pathway activation. Inhibition of either IL-23 by a specific neutralization antibody, or mTOR by rapamycin, or NF-κB by IKK-16, significantly reversed the autophagy suppression and ROS accumulation. These results demonstrate a key role for IL-23 in HT pathogenesis and provide a potential therapeutic strategy against IL-23 or its signalling pathway in HT.
TY - JOUR. T1 - Autophagy balances inflammation in innate immunity. AU - Deretic, Vojo. AU - Levine, Beth. PY - 2018/2/1. Y1 - 2018/2/1. N2 - Macroautophagy/autophagy is a homeostatic process with multiple effects on immunity. One of the pivotal contributions of autophagy in immunity is the cell autonomous control of inflammation. This property leads to systemic consequences and thereby influences the development of innate and adaptive immunity, which promotes or suppresses pathology in various disease contexts. In this review we focus on the intersections between autophagy and inflammasome activation, autophagy and interferons, and autophagy and inflammation in association with infection.. AB - Macroautophagy/autophagy is a homeostatic process with multiple effects on immunity. One of the pivotal contributions of autophagy in immunity is the cell autonomous control of inflammation. This property leads to systemic consequences and thereby influences the development of innate and adaptive ...
Cells undergo autophagy or self-eating as a means of recycling their constituents in order to maintain homeostasis. Autophagy is up regulated by stress, including amino acid deprivation for which it is best characterised. Upon amino acid starvation double or multiple lamellar vesicles termed autophagic vacuoles (AV) or autophagosomes appear throughout the cells cytoplasm. From their content they can be seen to have sequestered cytoplasm, often including organelles. Screens for autophagy defective mutants in Saccharomyces cerevisiae resulted in the AuTophaGy (ATG) genes. I have studied the ubiquitously expressed mammalian orthologue of Atg9p (Atg9Ll), a multi-spanning transmembrane protein shown to be essential in yeast for autophagy. I studied Atg9Ll in the hope that, as it is a multi-spanning transmembrane protein, it might provide clues as to the origin of the autophagosomal membranes. Initially addressing the proteins topology I show that both the N-and C-termini of Atg9L1 are cytosolic, ...
Cells of the Monocyte / Macrophage lineage are key players in innate and adaptive immunity. They eliminate pathogens through their phagocytic and antimicrobial properties, secretion of inflammatory and immunoregulatory cytokines, as well as their capacity to present foreign antigens to T lymphocytes in lymphoid tissues. The importance of M/Ms in the immune response require them to undergo strict regulation, which occurs, at least in part, through the control of monocytic cell survival. Autophagy is a ubiquitous cellular process by which cells degrade intracellular, cytoplasmic components via a network of interconnected vacuoles to carry out a variety of functions. Autophagy typically functions in maintaining cellular homeostasis and mitigating stresses. However, more recent studies have shown that autophagy may play a role in cell death. Our laboratory has previously found that the cytokine IFNγ can induce cell death in human monocytes in an autophagy-dependent manner. Conversely, IL-10 ...
Autophagy (Autofagia) Mohamed Elgendy MD, PhD Autophagy (Autofagia) Mohamed Elgendy MD, PhD [email protected] Auto+phagy Greek for Self Eating Autophagy = Recycling Types of Autophagy • 1-Macro-autophagy • 2-Micro-autophagy • 3-Chaperon-mediated autophagy Macro-autophagy 1-Induction Lysosome Autophagosome Fusion LC 3 LC3 II PE LC 3 LC 3 Phagophore 2-Nucleation Autolysosome LC3 I 3-Maturation Other types of Autophagy • Macro-autophagy Delivery of cytoplasmic cargo to the lysosome through the intermediary of a double membranebound vesicle, referred to as an autophagosome, that fuses with the lysosome to form an autolysosome. • Micro-autophagy Cytosolic components are directly taken up by the lysosome itself through invagination of the lysosomal membrane • Chaperon-mediated autophagy Targeted proteins are translocated across the lysosomal membrane in a complex with chaperone proteins (such as Hsc-70) that are recognized by the lysosomal membrane receptor LAMP-2A, resulting in their ...
OBJECTIVES The extent of autophagy in myocardium following persistent ischemia and the effects of insulin resistance and diabetes on cardiac autophagy following myocardial infarction (MI) have not been well elucidated. It is generally thought that autophagy reflects the nutritional status of cells, presumably alterable by diabetes. It has been conjectured that diminution of autophagy early after the onset of MI may preserve jeopardized myocardium thereby improving prognosis. METHODS Ten-week-old nondiabetic C57BL6 mice, 20-week-old diabetic and nondiabetic C57BL6 mice were subjected to MI for 4 weeks. Hearts from these mice were harvested and assayed for markers of autophagy. RESULT Hearts of 10-week-old C57BL6 mice subjected to 4 weeks of MI had similar levels of LC3-II, a protein indicator of autophagy, as measured by western blotting compared with hearts from sham operated controls. In 20-week-old C57BL6 mice rendered diabetic by feeding a high-fat diet, the amounts of autophagy were comparable
|p| Autophagy is an extremely old process during which long-lived proteins and cellular organelles are removed by means of lysosomes. Autophagy may be caused by cellular stress mechanisms. Research has proven that autophagy plays a key role in obtaining nutrients and adapting to the conditions of starvation. Owing to this, it takes part in maintaining homeostasis in cytoplasm and cell nucleus. This objective may be achieved through a number of ways. Depending on the manner in which a substrate connects with the lysosome, we can talk about macroautophagy and microautophagy. Additionally, some authors also distinguish a chaperone-mediated autophagy. The article presented below describes molecular mechanisms of each type of autophagy and focuses particularly on macroautophagy, which is the best understood of all the autophagy types.|/p|
The p53-inducible TIGAR protein functions as a fructose-2,6-bisphosphatase, promoting the pentose phosphate pathway and helping to lower intracellular reactive oxygen species (ROS). ROS functions in the regulation of many cellular responses, including autophagy--a response to stress conditions such as nutrient starvation and metabolic stress. In this study, we show that TIGAR can modulate ROS in response to nutrient starvation or metabolic stress, and functions to inhibit autophagy. The ability of TIGAR to limit autophagy correlates strongly with the suppression of ROS, with no clear effects on the mTOR pathway, and is p53 independent. The induction of autophagy in response to loss of TIGAR can function to moderate apoptotic response by restraining ROS levels. These results reveal a complex interplay in the regulation of ROS, autophagy and apoptosis in response to TIGAR expression, and shows that proteins similar to TIGAR that regulate glycolysis can have a profound effect on the autophagic response
Neutrophils, the essential components of the innate immune system, are recruited in large numbers to the pathogen site of entry. Several pathogens induce neutrophil autophagy; however, function of autophagic events during Leishmania parasite infection remain unknown. In this article, we report a finding that is new, to our knowledge, of how Leishmania-induced human polymorphonuclear neutrophil (hPMN) autophagy regulates the silent mode of parasite transfer to macrophages by influencing the engulfment of infected cells. Leishmania infection induced a time-dependent autophagy increase responsive to block by 3-methyladenine but sensitive to ULK1/2 inhibition only after 3 h. This suggested the prevalence of canonical autophagy during later hours, ULK1/2 inhibition being able to block only canonical autophagy. Interaction of Rubicon and Beclin-1 at 1 h postinfection affirmed the prevalence of noncanonical autophagy during early infection. There was a reduction in macrophage uptake of parasite-exposed ...
Presenilins are ubiquitous, intramembrane proteins that are known to have crucial functions in many cellular processes. Here we report the finding that endogenous, wild-type presenilins are critical mediators of cellular autophagy. Genetically ablating presenilins, together or independently, alters many key autophagic proteins and results in abnormal buildup in autophagosomes. Notably, increases in LC3-II, indicating a buildup of autophagosomes, were replicated with presenilin knockdown in neuroblastoma cells, demonstrating a role for presenilins in autophagy in multiple cell types. We found that presenilin-null cells have decreased proteolysis of long-lived proteins, even when autophagy is pharmacologically induced, suggesting that they have a buildup of autophagosomes as a result of dysfunction in autophagy after autophagosome completion. This conclusion was validated through the use of lysosomal inhibitors that did not cause additional buildup of autophagosomes in presenilin-null cells ...
Huang, S, et al. (2011) Inhibition of mTOR kinase by AZD8055 can antagonize chemotherapy-induced cell death through autophagy induction and down-regulation of p62/sequestosome 1. J. Biol. Chem.. 2011 Nov 18; 286(46):40002-12. PM ID: ...
Nuclear factor erythroid-2-related factor 2 (Nrf2) appears to exert either a protective or detrimental effect on the heart; however, the underlying mechanism remains poorly understood. Herein, we uncovered a novel mechanism for turning off the Nrf2-mediated cardioprotection and switching on Nrf2-mediated cardiac dysfunction. In a murine model of pressure overload-induced cardiac remodeling and dysfunction via transverse aortic arch constriction, knockout of Nrf2 enhanced myocardial necrosis and death rate during an initial stage of cardiac adaptation when myocardial autophagy function is intact. However, knockout of Nrf2 turned out to be cardioprotective throughout the later stage of cardiac maladaptive remodeling when myocardial autophagy function became insufficient. Transverse aortic arch constriction -induced activation of Nrf2 was dramatically enhanced in the heart with impaired autophagy, which is induced by cardiomyocyte-specific knockout of autophagy-related gene (Atg)5. Notably, Nrf2 ...
Cinnamic aldehyde (CA), a key flavor compound in cinnamon essential oil, has been identified as an anti-oxidant, anti-angiogenic, and anti-inflammatory material. Recently, the neuroprotective effects of CA have been reported in various neurodegenerative disorders, including Parkinsons disease (PD). In neurons, autophagy is tightly regulated, and consequently, the dysregulation of autophagy may induce neurodegenerative disorders. In the present study, we found that the selective dopaminergic neuronal death in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models was prevented by CA. Stimulation of microtubule-associated protein light chain 3 (LC3) puncta mediated by MPTP treatment was decreased by CA. Moreover, down-regulated p62 in the substantia nigra of MPTP mice was increased by administration of CA. Finally, we showed that blockage of autophagy using autophagy inhibitors protected the 1-methyl-4-phenylpyridinium (MPP⁺)-mediated death of BE(2)-M17 cells. ...
Author Summary Autophagy is an evolutionarily conserved process that sequestrates and delivers cytoplasmic macromolecules and organelles to the vacuoles or lysosomes for degradation. In plants, autophagy is involved in supplying internal nutrients during starvation and in promoting cell survival during senescence and during biotic and abiotic stresses. Arabidopsis NBR1 is a homolog of mammalian autophagy cargo adaptors P62 and NBR1. Disruption of Arabidopsis NBR1 caused increased sensitivity to a spectrum of abiotic stresses but had no significant effect on plant senescence, responses to carbon starvation, or resistance to a necrotrophic pathogen. NBR1 contains an ubiquitin-binding domain, and the compromised stress tolerance of autophagy mutants was associated with increased accumulation of NBR1 and ubiquitin-positive cellular protein aggregates in the insoluble protein fraction under stress conditions. Based on these results, we propose that NBR1 targets ubiquitinated protein aggregates most likely
TY - JOUR. T1 - Proteolytic self-digestion of bovine erythrocyte membranes. AU - Gaczyńska, Maria. AU - Bartosz, Grzegorz. AU - Rosin, Janusz. AU - Soszyński, Mirosław. N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 1985. Y1 - 1985. N2 - 1. 1. Self-digestion of bovine erythrocyte membrane proteins was studied in isolated membrane preparations during prolonged incubation at 37 C. 2. 2. Protcase activities associated with the membrane result in progressive degradation of all main erythrocyle membrane proteins, in particular spectrin and Band 3. and formation of lower molecular weight products which have been tentatively assigned to parent molecules. 3. 3. Membrane protein self-digestion occurs in a broad pH range (2-11), is inhibited by increased ionic strength and by inhibitors of metalloproteases. cysteine and serine proteases. and activated by low concentrations of SDS. 4. 4. Self-digestion also takes place in NaOH-stripped erythrocyte membranes. 5. 5. The ...
The Nobel Assembly at Karolinska Institutet on 3 October 2016 decided to award the 2016 Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi.. Ohsumi is bestowed with the prize for his discoveries of mechanisms for autophagy. He discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components.. What is autophagy?. • Autophagy is the natural, destructive mechanism that disassembles, through a regulated process, unnecessary or dysfunctional cellular components.. • It allows the orderly degradation and recycling of cellular components.. • During this process, targeted cytoplasmic constituents are isolated from the rest of the cell within a double-membraned vesicle known as an autophagosome.. • The autophagosome then fuses with a lysosome and the contents are degraded and recycled.. • Three different forms of autophagy are commonly described as macroautophagy, microautophagy and chaperone-mediated autophagy.. • The name ...
Autophagy is a survival mechanism against stress It involves the degradation of cellular components to generate energy through the lysosome However autophagy overactivation under continuous stress leads to cell apoptosis Recombinant thrombomodulin protects vascular endothelial cells and reduces the risk of atherosclerosis Treatment with recombinant thrombomodulin increases endothelial cells Akt activation which also regulates autophagy initiation We hypothesized that recombinant thrombomodulin might influence vascular endothelial cell behaviors through regulating autophagy First we observed the expression of autophagy related proteins in endothelial cells under starvation with and without recombinant thrombomodulin treatment In starvation we found that autophagy initiation signal was induced and LC3-II and Atg5 expression contributing to autophagosomal formation increased After treating recombinant thrombomodulin Akt and mTOR was activated and autophagy-related proteins expression were inhibited ...
Autophagy is an essential recycling pathway implicated in neurodegeneration either as a pro-survival or a pro-death mechanism. Its role after axonal injury is still uncertain. Axotomy of the optic nerve is a classical model of neurodegeneration. It induces retinal ganglion cell death, a process also occurring in glaucoma and other optic neuropathies. We analyzed autophagy induction and cell survival following optic nerve transection (ONT) in mice. Our results demonstrate activation of autophagy shortly after axotomy with autophagosome formation, upregulation of the autophagy regulator Atg5 and apoptotic death of 50% of the retinal ganglion cells (RGCs) after 5 days. Genetic downregulation of autophagy using knockout mice for Atg4B (another regulator of autophagy) or with specific deletion of Atg5 in retinal ganglion cells, using the Atg5flox/flox mice reduces cell survival after ONT, whereas pharmacological induction of autophagy in vivo increases the number of surviving cells. In conclusion, ...
TY - JOUR. T1 - Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. AU - Koga, Hiroshi. AU - Cuervo, Ana Maria. PY - 2011/7. Y1 - 2011/7. N2 - Chaperone-mediated autophagy (CMA) contributes to selective degradation of individual soluble proteins in lysosomes. Unique to this type of autophagy is the fact that proteins reach the lysosomal lumen for degradation by directly crossing the lysosomal membrane, in contrast with the vesicle-mediated delivery characteristic of the other types of autophagy. These two characteristics - selective targeting and direct translocation of substrates - determine the contribution of CMA to different physiological functions and the type of pathological conditions associated with CMA dysfunction. In this review, we briefly revise recent findings on the molecular mechanisms behind CMA function, and describe the physiological relevance of the selective lysosomal degradation through this pathway. We also comment on the cellular consequences ...
TY - JOUR. T1 - Synthetic lethal interaction of CDK inhibition and autophagy inhibition in human solid cancer cell lines. AU - Okada, Yoshinari. AU - Kato, Shunsuke. AU - Sakamoto, Yasuhiro. AU - Oishi, Takayuki. AU - Ishioka, Chikashi. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 2017. Y1 - 2017. N2 - Cell cycle control is a promising target in cancer treatments, and some small-molecule cyclin-dependent kinase (CDK) inhibitors have exhibited clinical effectiveness. However, no biomarkers predictive of efficacy have been developed. Recent studies have revealed that CDK inhibitor (CKI) proteins, such as p27 and p16, also induced cytoprotective autophagy in cancer cells. However, it is unclear whether small-molecule CKIs also induce autophagy in solid tumors, as induced autophagy promotes cancer cell survival. In this study, we revealed that a CDK4 inhibitor and a CKI with a broad range of targets (flavopiridol) induced autophagy in some, but not all, solid cancer cell ...
Histone methylation plays an important role in gene transcription and chromatin organization and is linked to the silencing of a number of critical tumor suppressor genes in tumorigenesis. G9a is a histone methyltransferase (HMTase) for histone H3 lysine 9. In this study, we investigated the role of G9a in neuroblastoma tumor growth together with the G9a inhibitor BIX01294. The exposure of neuroblastoma cells to BIX01294 resulted in the inhibition of cell growth and proliferation, and BIX01294 treatment resulted in the inhibition of the tumorigenicity of neuroblastoma cells in NOD/SCID mice. Therefore, G9a may be a potential therapeutic target in neuroblastoma. Moreover, we found several specific characteristics of autophagy after BIX01294 treatment, including the appearance of membranous vacuoles and microtubule-associated protein light chain 3 (LC3B). Similar results were observed in G9a-knockdown cells. In conclusion, our results demonstrated that G9a is a prognostic marker in neuroblastoma, and
Macrophage derived foam cells in atherosclerotic plaques are the major factor responsible for the pathogenesis of atherosclerosis (AS). During advanced AS, macrophage-specific macroautophagy/autophagy is dysfunctional. 1, 25-dihydroxy vitamin D3 (VitD3) and its receptor VDR (vitamin D receptor) are reported to inhibit foam cell formation and induce autophagy; however, the role of VitD3-VDR-induced autophagy and foam cell formation in AS has not been explored. Here we find that VitD3 significantly recovered oxidized low-density lipoprotein-impaired autophagy, as well as increased autophagy-mediated lipid breakdown in mouse bone marrow-derived macrophages and human monocyte-derived macrophages, thus inhibiting the conversion of macrophages into foam cells. Importantly, VitD3 functions through its receptor VDR to upregulate autophagy and attenuate the accumulation of lipids in macrophages. Moreover, this study is the first occasion to report the interesting link between VitD3 signaling and ...
Autophagy occurs in cells that undergoing nutrient deprivation. Glycolysis rapidly supplies energy for the proliferation of cancer cells. Cardamonin inhibits proliferation and enhances autophagy by mTORC1 suppression in ovarian cancer cells. Here, we investigate the relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression. Treated with indicated compounds, ATP content and the activity of hexokinase (HK) and lactate dehydrogenase (LDH) were analyzed by the assay kits. Autophagy was detected by monodansylcadaverin (MDC) staining. The relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression was analyzed by Western blot. We found that cardamonin inhibited the lactate secretion, ATP production, and the activity of HK and LDH. The results demonstrated that cardamonin enhanced autophagy in SKOV3 cells, as indicated by acidic compartments accumulation, microtubule-associated protein 1 Light Chain 3-II (LC3-II) and lysosome
Objective:To investigate the effects of autophagy on vascular smooth muscle cell of rat in vitro and provide a new compelling evidence for prevention of the proliferation of vascular smooth muscle cel
Orexin A (OXA) is a neuroprotective peptide that exerts protective effects on multiple physiological and pathological processes. Activation of autophagy is linked to the occurrence of cerebral ischemia-reperfusion injury (CIRI); however, its function remains incompletely understood. In this study, OXA was sought to exert its neuroprotective role by regulating autophagy in oxygen and glucose deprivation and reoxygenation (OGD/R) model and middle cerebral artery occlusion (MCAO) model of rats, and to elucidate the underlying molecular mechanisms. Acridine orange (AO) staining was used to evaluate autophagic vacuoles. Cell viability was measured by CCK8. The levels of p-ERK1/2, t-ERK1/2, p-mTOR, LC3B, Beclin 1, and p62 were evaluated by western blotting. Apoptosis rate was detected by Hoechst 33342 staining and Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL). OXA treatment alleviated neuronal apoptosis and significantly inhibited autophagy activity. Mechanistically, OXA ...
Amitriptyline is a tricyclic antidepressant commonly prescribed for major depressive disorders, as well as depressive symptoms associated with various neurological disorders. A possible correlation between the use of tricyclic antidepressants and the occurrence of Parkinsons disease has been reported, but its underlying mechanism remains unknown. The accumulation of misfolded protein aggregates has been suggested to cause cellular toxicity and has been implicated in the common pathogenesis of neurodegenerative diseases. Here, we examined the effect of amitriptyline on protein clearance and its relevant mechanisms in neuronal cells. Amitriptyline exacerbated the accumulation of abnormal aggregates in both in vitro neuronal cells and in vivo mice brain by interfering with the (1) formation of aggresome-like aggregates and (2) autophagy-mediated clearance of aggregates. Amitriptyline upregulated LC3B-II, but LC3B-II levels did not increase further in the presence of NH4Cl, which suggests that
Breast cancer is the most common solid cancer that affects female population globally. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate post-transcriptional modification of multiple downstream genes. Autophagy is a conserved cellular catabolic activity that aims to provide nutrients and degrade un-usable macromolecules in mammalian cells. A number of in vitro, in vivo and clinical studies have reported that some miRNAs could modulate autophagy activity in human breast cancer cells, and these would influence human breast cancer progression and treatment response. Therefore, this review was aimed to discuss the roles of autophagy-regulating miRNAs in influencing breast cancer development and treatment response. The review would first introduce autophagy types and process, followed by the discussion of the roles of different miRNAs in modulating autophagy in human breast cancer, and to explore how would this miRNA-autophagy regulatory process affect the disease progression or treatment
Lymphangioleiomyomatosis LAM, a disease that primarily affects women, is characterized by cystic lung destruction. LAM results from the proliferation of LAM cells that harbor mutations in the TSC1 or TSC2 genes, leading to activation of the mammalian target of rapamycin complex 1 mTORC1. Recently, sirolimus rapamycin has been shown to stabilize lung function decline and decrease angiomyolipoma tumor size. Discontinuation of therapy results in progression of lung function decline and tumor growth, suggesting that continuous use is required to maintain its beneficial effects. Autophagy self eating is a mechanism by which tumor cells recycle proteins and organelles. Blocking TORC1, a known autophagy inhibitor, with rapamycin increases autophagy and promotes survival of TSC2-deficient cells. The Sirolimus and Autophagy Inhibition in LAM SAIL trial is a phase I clinical trial to test the safety and tolerability of a combination of hydroxychloroquine and sirolimus in women with LAM. We will measure the effect
Objective(s): To investigate the role of autophagy in advanced glycation end products (AGEs)-induced proliferation and migration in rat vascular smooth muscle cells (VSMCs).Materials and Methods: After culture, VSMCs were treated with 0, 1, 10, and 100 μg/ml concentrations of AGEs. Autophagy specific protein light chain 3 (LC3)-I/II was determined by western blotting, autophagosomes were observed with electron microscopy, cell proliferation was quantified using the methyl thiazolyl tetrazolium (MTT) assay, and cell migration was evaluated using Transwell migration and scratch assays. Results: Compared to the control group, the level of LC3- II/I in AGEs treatment group was up-regulated, and the number of autophagosomes was also increased. Furthermore, in concentration of 100 μg/ml AGEs, the extent of proliferation and migration was significantly increased compared to the control group. However, pretreating cells with autophagy inhibitor 3-MA could attenuate these effects.Conclusion: Our study
We demonstrate that Sirt1 activity is necessary for the induction of starvation-induced autophagy. In addition, transiently augmenting wild-type Sirt1 activity but not a deacetylase-inactive mutant of Sirt1 is sufficient to activate autophagy in cells even in the presence of nutrients. Essential components of the autophagy machinery interact with Sirt1, and the absence of Sirt1 dramatically increases the level of acetylation for multiple Atg-related gene products. Consistent with a requirement for Sirt1 in the execution of autophagy, embryos and neonatal mice lacking Sirt1 accumulate abnormal organelles, especially mitochondria, demonstrate increased levels of p62 and the activation of AMPK. In addition, the in utero delivery of pyruvate allows for prolonged survival of Sirt1−/− pups. The latter results need to be interpreted with caution because there is a growing body of data suggesting that ethyl pyruvate administration might be beneficial in a number of in vivo experimental stress ...
Alzheimers disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia in the aging population. Currently, there is no cure for AD. The hallmark of AD consists of extracellular amyloid plaques, mainly composed of amyloid beta (Ab) peptides (especially Ab1-42), and neurofibrillary tangles, mainly composed of hyperphosphorylated tau. Ab and tau can interact with each other synergistically to trigger neurotoxicity. Autophagy is a lysosomal degradation process that mediates the cellular clearance of misfolded/aggregated proteins/peptides including Ab and tau. Malfunctions in autophagy have been observed in several neurodegenerative diseases, and it has been proposed that promoting cellular autophagy may be an effective strategy to treat AD and other related neurodegenerative diseases. Acyl-CoA: cholesterol acyltransferase (ACAT) converts free cholesterol to cholesteryl esters and plays important roles in cellular cholesterol homeostasis. Previous work from this and ...
Autophagy was first described in 1962 when researchers noted an increase in the number of lysosomes (the part of the cell that destroys stuff) in rat liver cells after infusing glucagon. The Nobel prize winning scientist Christian de Duve coined the term autophagy. Damaged sub cellular parts and unused proteins become marked for destruction and then sent to the lysosomes to finish the job.. One of the key regulators of autophagy is the kinase called mammalian target of rapamycin (mTOR). When mTOR is activated, it suppresses autophagy, and when dormant, it promotes it.. Nutrient deprivation is the key activator of autophagy. Remember that glucagon is kind of the opposite hormone to insulin. Its like the game we played as kids - opposite day. If insulin goes up, glucagon goes down. If insulin goes down, glucagon goes up. As we eat insulin goes up and glucagon goes down. When we dont eat (fast) insulin goes down and glucagon goes up. This increase in glucagon stimulates the process of ...
Background: Mitochondrial permeabilization provokes cardiomyocyte death, and causes adverse left ventricular remodeling in cardiac-restricted TNF transgenic mice (MHCsTNF). Autophagy, a lysosomal degradative pathway, is essential for removal of ubiquitin-tagged damaged mitochondria. Our prior work suggests that TNF receptor associated factor-2 (TRAF2), a multifunctional protein with E3 ubiquitin ligase activity, facilitates removal of damaged mitochondria. The role of TRAF2 vis-à-vis PARKIN, another E3 ubiquitin ligase essential for mitophagy, is unknown.. Methods and Results: MHCsTNF hearts and TNF-treated neonatal rat cardiac myocytes (NRCMs) demonstrate upregulation of both TRAF2 and PARKIN, with increased evidence for mitochondrial autophagy and reduced mitochondrial mass. To evaluate the role of TRAF2 and PARKIN in autophagic removal of damaged mitochondria, we employed gain-of-function and loss-of-function approaches; and assessed mitochondrial mass with nonyl-acridine orange fluorescence ...
Autophagy is a major pathway for degradation of cytoplasmic components, and is induced by some apoptotic stimuli mostly in cancer cells under the condition in which apoptosis is blocked. Ligation of the B cell antigen receptor (BCR) induces apoptosis and plays a crucial role in self-tolerance. However, whether BCR ligation induces autophagy is not clear. Here, we demonstrate that autophagosomes are extensively formed in normal mouse B cells as well as the WEHI-231 B cell line upon induction of BCR ligation-induced apoptosis regardless of whether apoptosis is blocked by overexpression of Bcl-2. In contrast, autophagosomes were not formed during apoptosis of spleen B cells cultured with medium alone or in BCR-ligated BAL17 cells which do not undergo apoptosis. Moreover, autophagy is not induced when apoptotic BCR signaling is abrogated by CD40 signaling. These results indicate that autophagy is induced specifically by apoptotic BCR signaling even in unmanipulated normal B cells.
TY - JOUR. T1 - Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor. AU - Feng, Rentian. AU - Wang, Shiow Y.. AU - Shi, Ying Hong. AU - Fan, Jia. AU - Yin, Xiao-Ming. PY - 2010/4/14. Y1 - 2010/4/14. N2 - The present study was performed to determine whether anthocyanins could trigger different modes of cell death in different cancers. It was found that whereas cyanidin-3-rutinoside and delphinidin could induce apoptosis in leukemia cells, they caused growth retardation in hepatocellular carcinoma cells (HCC), which was accompanied with a significant cellular vacuolization. The latter was likely caused by macroautophagy and was completely suppressed by 3-methyladenine, an inhibitor of class III phosphoinositide 3-kinase that is important for autophagy activation, and by bafilomycin A1, which blocks lysosomal degradation. Delphinidin induced significant lipidation of LC3, an indication of macroautophagy, which was also suppressed ...
Expression of COP9 signalosome subunit 3 (COPS3), an oncogene overexpressed in osteosarcoma, has been demonstrated to be significantly correlated with tumor metastasis. However, the underlying mechanism by which COPS3 promotes metastasis of osteosarcoma and its role in autophagy remain unknown. The expression of COPS3 was detected in primary osteosarcoma tissues and matching lung metastasis tissues by immunohistochemistry (IHC). The effect of COPS3 on the metastasis of osteosarcoma cells was investigated by transwell, wound healing assays and animal studies. Indicated proteins was analyzed by western blotting when COPS3 was knockdown or overexpressed. The COPS3 Interacting protein was determined by immunoprecipitation assay. The relationship between COPS3 and autophagy was detected by western blotting and immunofluorescence. We found that knockdown of COPS3 significantly reduced the lung metastasis of osteosarcoma cells in a mouse model, coinciding with downregulation of mitogen-activated protein kinase
Pharmacological activation of peroxisome proliferator activated receptor alpha (PPARα) is an effective treatment for dyslipidaemia. Autophagy dysfunction has been observed in disorders of lipid metabolism, especially in the liver. In this study, we have identified the PPARα as a potential inhibitor of the autophagy pathway, reducing the correlate of forkhead box protein O1 (FoxO1) and enhancing endoplasmic reticulum (ER) stress. This study was performed in chow (CH) diet fed mice treated with the PPARα agonist, fenofibrate (FB, 100mg/kg/day). PPARα-induced CH displayed a significant suppression of autophagy action (p,0.01 for all), which is indicated by a reduction in key autophagy proteins Atg5, Atg7 and p62 (p,0.05; FB vs. untreated). Moreover, the inhibited autophagy pathway abolished FoxO1 (p,0.01 FB vs. untreated). Interestingly, this suppressed autophagy is associated with enhanced activation of unfolded protein response (UPR) signalling, namely IRE/XBP1 and PERK/eIF2α, indicating ER ...
TY - JOUR. T1 - P62 Stages an Interplay Between the Ubiquitin-Proteasome System and Autophagy in the Heart of Defense Against Proteotoxic Stress. AU - Su, Huabo. AU - Wang, Xuejun. PY - 2011/11/1. Y1 - 2011/11/1. N2 - As exemplified by desmin-related cardiomyopathy and myocardial ischemia/reperfusion injury, proteasome functional insufficiency plays an essential pathogenic role in the progression of cardiac diseases with elevated proteotoxic stress. Upregulation of p62/SQSTM1 and increased selective autophagy in cardiomyocytes may protect against proteotoxic stress in the heart. p62 may serve as a proteotoxic stress sensor, promote segregation and degradation of misfolded proteins by autophagy, and mediate the cross talk between the ubiquitin-proteasome system and autophagy.. AB - As exemplified by desmin-related cardiomyopathy and myocardial ischemia/reperfusion injury, proteasome functional insufficiency plays an essential pathogenic role in the progression of cardiac diseases with elevated ...
AbstractThe ubiquitin-proteasome system and macroautophagy are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for the treatment of cancer. In this study, we show that proteasome inhibitor MG-132 suppressed gastric cancer cell proliferation and induced macroautophagy. The induction of macroautophagy was evidenced by the formation of LC3(+) autophagosomes and the accumulation of acidic vesicular organelles and autolysosomes and was accompanied by the suppression of mammalian target of rapamycin complex 1 activity. Abolition of macroautophagy by knockdown of Class III phosphatidylinositol-3 kinase Vps34 or ATG5/7 sensitized gastric cancer cells to the antiproliferative effect of MG-132 by promoting G(2)/M cell cycle arrest. In addition, MG-132 increased ERK phosphorylation whose inhibition by MEK inhibitor significantly enhanced the antiproliferative effect of proteasome inhibition. To conclude, this study ...
GSK461364 Clash of Curiosity No potential issues of curiosity had been revealed. Personal references 1. Baehrecke EH. Autophagy: dual jobs in lifestyle and loss of life? Nat Rev Mol Cell Biol. 2005;6(6):505C510. [PubMed] 2. Mizushima D. Autophagy: procedure and function. Genetics & advancement. 2007;21(22):2861C2873. [PubMed] 3. Levine T, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27C42. [PMC free of charge content] [PubMed] 4. Mizushima D, Levine T, Cuervo Have always been, Klionsky DJ. Autophagy battles disease through mobile self-digestion. Character. 2008;451(7182):1069C1075. [PMC free of charge content] [PubMed] 5. Levine T, Klionsky DJ. Advancement by self-digestion: molecular systems and natural features of autophagy. Developmental cell. 2004;6(4):463C477. [PubMed] 6. Hsu PP, Sabatini DM. Cancers cell fat burning capacity: Warburg and beyond. Cell. 2008;134(5):703C707. [PubMed] 7. Mathew Ur, Light Age. Autophagy, tension, and cancers fat burning capacity: what ...
In the adult brain, programmed death of neural stem cells is considered to be critical for tissue homeostasis and cognitive function and is dysregulated in neurodegeneration. Previously, we have reported that adult rat hippocampal neural (HCN) stem cells undergo autophagic cell death (ACD) following insulin withdrawal. Because the apoptotic capability of the HCN cells was intact, our findings suggested activation of unique molecular mechanisms linking insulin withdrawal to ACD rather than apoptosis. Here, we report that phosphorylation of autophagy-associated protein p62 by AMP-activated protein kinase (AMPK) drives ACD and mitophagy in HCN cells. Pharmacological inhibition of AMPK or genetic ablation of the AMPK alpha 2 subunit by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing suppressed ACD, whereas AMPK activation promoted ACD in insulin-deprived HCN cells. We found that following insulin withdrawal AMPK phosphorylated p62 at a novel site, ...
Histone deacetylases regulate the processes of differentiation, cell cycle, and apoptosis through the deacetylation of epigenetic, indirect epigenetic and nonepigenetic substrates. However, the cellular and molecular mechanisms controlled by individual HDAC isozymes are poorly understood (8, 30, 48). Here, we report a critical function of HDAC10 in regulating autophagic flux and cell survival. The HDAC class IIb family includes HDAC6 and HDAC10. Whereas numerous publications on HDAC6 function as a microtubule-associated deacetylase involved in the response to misfolded protein stress via degradation by autophagy have been published (49⇓⇓-52), little is known about the molecular and cellular function of HDAC10. HDAC10 has been reported to be involved in melanogenesis via repressor deacetylation (47) and in thioredoxin up-regulation in gastric cancer cells (53). A HDAC10 knockout phenotype has yet to be described. Thus, the identification of HDAC10 as an important regulator of autophagy and ...
Aggregation of misfolded proteins and the associated loss of neurons are considered as a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntingtons disease, Alzheimers disease, Parkinsons disease, Creutzfeld-Jacob disease and Picks disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognized various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increase protein aggregation in HeLa cells and morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in ...
TY - JOUR. T1 - Dysregulation of TFEB contributes to manganese-induced autophagic failure and mitochondrial dysfunction in astrocytes. AU - Zhang, Ziyan. AU - Yan, Jingqi. AU - Bowman, Aaron B.. AU - Bryan, Miles R.. AU - Singh, Rajat. AU - Aschner, Michael. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Epidemiological and clinical studies have long shown that exposure to high levels of heavy metals are associated with increased risks of neurodegenerative diseases. It is widely accepted that autophagic dysfunction is involved in pathogenesis of various neurodegenerative disorders; however, the role of heavy metals in regulation of macroautophagy/autophagy is unclear. Here, we show that manganese (Mn) induces a decline in nuclear localization of TFEB (transcription factor EB), a master regulator of the autophagy-lysosome pathway, leading to autophagic dysfunction in astrocytes of mouse striatum. We further show that Mn exposure suppresses autophagic-lysosomal degradation of mitochondria and induces ...
Objective To research if ICI 182,780 (fulvestrant), a selective estrogen receptor alpha/beta (ER/ER) antagonist, and G-1, a selective G-protein-coupled receptor (GPER) agonist, may induce autophagy in breasts cancers cell lines MCF-7 and SKBr3 potentially, and exactly how G-1 affects cell viability. the cell lines. On the other hand, ICI 182,780 and G-1 didnt lower cell viability of SKBr3 cells or induce development of acidic vesicular organelles, which corresponds to the ultimate step from the autophagy procedure within this cell range. Conclusion The result of ICI 182,780 on raising acidic vesicular organelles in estrogen receptor-positive breasts cancer cells is apparently connected with its inhibitory influence on estrogen receptors, and GPER will notseem to be engaged. Understanding these systems might information further investigations of the receptors participation in cellular procedures of breasts cancers level of resistance. under opinion amount 1748/10. Reagents DMEM/F12, fetal bovine ...
Special to The Dallas Examiner. A team led by UT Southwestern researchers has identified a key gene necessary for cells to consume and destroy viruses. The findings, reported online today in Nature, could lead to ways to manipulate this process to improve the immune systems ability to combat viral infections, such as those fueling the ongoing COVID-19 pandemic.. Scientists have long known that cells use a process called autophagy to rid themselves of unwanted material. Autophagy, which translates as self-eating, involves isolating cellular garbage in double-layered vesicles called autophagosomes, which are then fused with single-layered vesicles known as lysosomes to degrade the materials inside and recycle them into building blocks for other uses.. This process helps cells discard old or defective organelles and protein complexes, bacteria and viral invaders. For a variety of cellular refuse tasks, researchers have identified clear pathways by which cells initiate and regulate autophagy. But ...
Background The sialidase Neu2 is a cytosolic enzyme which is fully expressed in mature muscle myofibers. Methods To investigate Neu2 expression during muscle atrophy, we employed an in vitro model consisting of terminally differentiated C2C12 myotubes exposed to different pro-atrophic stimuli that triggered catabolic pathways involved in proteasome activation or autophagy. Results Neu2 expression was unchanged in myotubes treated with TNF-alpha, a cytokine known to activate the proteasome. However, Neu2 transcript levels and enzymatic activity were downregulated in starved or dexamethasone-treated myotubes that showed proteosomal activation and several hallmarks of macroautophagy, such as formation of autophagosomes, the accumulation of LC3 dots and bulk degradation of long-lived proteins. Neu2 activity and protein levels were rescued upon cotreatment with the lysosomotropic agent NH4Cl, the autophagy inhibitor 3-methyladenine or cathepsin inhibitors, as well as by insulin administration, but ...
The increase in LC3 flux and LLPD after Rab7b knockdown, together with the increase in size of LC3‐positive vesicles, suggests that sequestration of content into autophagosomes should also be increased. To investigate this, we measured the transfer of the autophagic cargo marker enzyme lactate dehydrogenase (LDH) from the cytosol to autophagosomes [36]. In this assay, BafA1 is added to prevent autolysosomal degradation of LDH, thus allowing the assessment of autophagic sequestration activity per se, instead of the net effect of autophagic sequestration and degradation.. Rab7b depletion led to a significant increase in LDH sequestration under starvation conditions, as well as after treatment with Torin1 (more than 1.5‐fold increase and twofold increase respectively; Fig 4E). Expression of HA‐Rab7b after Rab7b silencing significantly reversed the effect of Rab7b depletion on LDH sequestration, demonstrating the specificity of the Rab7b siRNA (Fig 4E). Of note, we observed a tendency of ...
Methods and Results: Using an autophagosome reporter and determining changes in LC3-II protein levels in response to lysosomal inhibition, we found significantly increased autophagic flux in mouse hearts with transgenic overexpression of a DRC-linked mutant desmin. Similarly, autophagic flux was increased in cultured neonatal rat ventricular myocytes (NRVMs) expressing a mutant desmin. Suppression of autophagy by 3-methyladenine increased, whereas enhancement of autophagy by rapamycin reduced the ability of a comparable level of mutant desmin overexpression to accumulate ubiquitinated proteins in NRVMs. Furthermore, p62 mRNA and protein expression was significantly upregulated in cardiomyocytes by transgenic overexpression of the mutant desmin or CryABR120G both in intact mice and in vitro. The p62 depletion impaired aggresome and autophagosome formation, exacerbated cell injury, and decreased cell viability in cultured NRVMs expressing the misfolded proteins.. ...
Aging is the main risk factor for the development of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal lung disorder. Although the pathogenic mechanisms are uncertain, endoplasmic reticulum (ER) stress and impaired proteostasis that have been linked with aging are strongly associated with the pathogenesis of IPF. Using the Atg4b-deficient mice as a model, that partially reproduces the autophagy deficient conditions reported in aging and IPF lungs, we show for the first time how autophagy impairment and ER stress induction, contribute simultaneously to development of lung fibrosis in vivo. Increased expression of ER stress markers, inflammation and apoptosis of alveolar epithelial cells were observed in Atg4b-deficient mice compared to WT mice, when treated with the ER stress inducer tunicamycin. After tunicamycin treatment, Atg4b null lungs showed accumulation of its substrate LC3-I, demonstrating that these mice failed to induce autophagy despite the ER stress conditions. We also
Summary Autophagy, a lysosomal degradation pathway in which the cell digests its own components, is an essential biological pathway that promotes organismal health and longevity and helps combat cancer and neurodegenerative diseases. Accordingly, the 2016 Nobel Prize in Physiology or Medicine was awarded for research in autophagy. Although autophagy has been extensively studied from yeast to mammals, the molecular events that underlie its induction and progression remain elusive. A highly conserved protein kinase, Atg1, plays a unique and essential role in initiating autophagy, yet despite this pivotal importance it has taken over twenty years for its first downstream target to be discovered. However, whilst our identification of the autophagy related membrane protein Atg9 as the first Atg1 substrate is an important advance, the molecular mechanisms that enable the extensive remodelling of cellular membranes that occurs during autophagy is still completely undefined. A detailed knowledge of the ...
Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), rely heavily on the availability of endoplasmic reticulum (ER) membranes throughout their lifecycle and degradation of ER membranes restricts flavivirus replication. Accordingly, DENV and ZIKV restrict ER turnover by protease-mediated cleavage of reticulophagy regulator 1 (RETREG1), also known as FAM134B, an autophagy receptor responsible for targeted ER sheet degradation. Given that the induction of autophagy may play an important role in flavivirus replication, the antiviral role of RETREG1 suggests specialized autophagic pathways may have differential effects on the flavivirus lifecycle. We previously identified BPI Fold Containing Family B Member 3 (BPIFB3) as a regulator of autophagy that negatively controls enterovirus replication. Here, we show that in contrast to enteroviruses, BPIFB3 functions as a positive regulator of DENV and ZIKV infection and that its RNAi-mediated silencing inhibits the formation of viral ...
Esophageal carcinoma is a malignancy that severely threatens human health, with a high incidence rate and a low 5‑year survival rate. Resistance to chemotherapy frequently emerges during its treatment, partly due to the induction of autophagy. Therefore, targeting autophagy may be a promising therapeutic approach for the treatment of esophageal carcinoma. In the present study, it was investigated how chloroquine (CQ) can influence the growth ability and biological behaviors of EC109 esophageal squamous carcinoma cells in vitro, as well as the potential molecular mechanisms behind its activity. It was demonstrated that CQ could suppress the growth and proliferation of EC109 cells in a time‑ and dose‑dependent manner; migration and colony formation abilities were also inhibited by CQ. Furthermore, subsequent to the exposure to CQ, the number of autophagosomes was clearly increased in EC109 cells overexpressing green fluorescent protein tagged‑light chain (LC)3 when observed by fluorescence ...
TAMPA, Fla (Oct. 12, 2020) - In a healthy brain, the multistep waste clearance process known as autophagy routinely removes and degrades damaged cell components - including malformed proteins like tau and toxic mitochondria. This cellular debris would otherwise pile up like uncollected trash to drive the death of brain cells (neurons), ultimately destroying cognitive abilities like thinking, remembering and reasoning in patients with Alzheimers and certain other neurodegenerative diseases.. The protein p62, a selective autophagy cargo receptor, plays a major role in clearing misfolded tau proteins and dysfunctional mitochondria, the energy powerhouse in all cells including neurons. Through autophagy (meaning self-eating in Greek) old or broken cellular material is ultimately digested and recycled in lysosomes, membrane-bound structures that work like mini-waste management plants.. Now, neuroscientists at the University of South Florida Health (USF Health) Byrd Alzheimers Center report for ...
It is confirmed that adipose-derived stem cells (ADSCs) transplantation effectively relieves kidney fibrosis and type 2 diabetes disease in mice. Currently, exosome from urine-derived stem cells (USCs) can protect type 1 diabetes-mediated kidney injury and attenuate podocyte damage in diabetic nephropathy (DN). Exosome derived from USCs has evolved into the strategy for DN treatment, but the role of ADSCs-derived exosome (ADSCs-Exo) in DN remains unclear. The present study is aimed to investigate the therapeutic action and molecular mechanism of ADSCs-derived exosome on DN. ADSCs and exosome were authenticated by immunofluorescence and flow cytometry. Morphology and the number of exosome were evaluated by electron microscope and Nanosight Tracking Analysis (NTA), respectively. Cell apoptosis was assessed using flow cytometry. Podocyte autophagy and signaling transduction were measured by immunofluorescence and immunoblotting. Dual Luciferase Reporter assay was employed to detect the regulatory
TY - JOUR. T1 - Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor-kappa B activity. AU - Krosch, Tara C.K.. AU - Sangwan, Veena. AU - Banerjee, Sulagna. AU - Mujumdar, Nameeta. AU - Dudeja, Vikas. AU - Saluja, Ashok K.. AU - Vickers, Selwyn M.. PY - 2013/4. Y1 - 2013/4. N2 - Background: Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. We assessed triptolide as a potential therapy. Methods: SH-SY5Y and IMR-32 neuroblastoma cell lines were treated with triptolide. Viability, intracellular calcium, caspase activation, protein, and mRNA levels were measured. Autophagy was evaluated with confocal microscopy. Nuclear factor-kappa B (NF-κB) activation was measured using a dual luciferase assay. Results: Triptolide treatment resulted in death in both cell lines within 72 hours, with sustained increases in intracellular calcium. IMR-32 cells underwent cell death by ...
The current report highlights LAMP-2 as a ubiquitously expressed protein of the CNS. In addition to its established role as a receptor for CMA, the function of LAMP-2 in the brain is not yet well defined. Absence of LAMP-2 in brain, especially within the subiculum and CA3 region of the hippocampus, caused pronounced inflammation as well as perturbed lysosomal activity and autophagy indicated by intraneuronal lipid storage, accumulation of autophagic vacuoles and neuronal degeneration in a subpopulation of neurons. Hippocampal neurons are particularly vulnerable to lysosomal storage induced degeneration as highlighted in various mouse models with lysosomal dysfunction [48,49] and in Alzheimer and Parkinson`s disease as well as dementia with Lewy bodies. To some extent this vulnerability can be explained by regional differences in the expression profile of proteins that can induce neurotoxicity under certain pathophysiological conditions such as aggregation of α-syn and amyloid-β. Interestingly, ...
As demonstrated by the 2016 Nobel Prize winner, Yoshinori Ohsumi, autophagy is a fundamental process vital to cellular health. The molecular processes and signalling pathways controlling autophagy include numerous autophagy-related (Atg) genes, important stress-inducible intracellular protein, such as p62/A170/SQSTM1 and autophagosome localizing proteins such as LC3, among many others making this a complex network of control.. ...
Background Resistance to adjuvant radiotherapy is a major cause of treatment failure in patients with glioblastoma (GBM). Autophagy inhibitors have been shown to enhance the efficacy of radiotherapy for certain solid tumors. However, current inhibitors do not penetrate the blood-brain-barrier (BBB). Here, we assessed the radiosensitivity effects of the antipsychotic drug trifluoperazine (TFP) on GBM in vitro and in vivo. Methods U251 and U87 GBM cell lines as well as GBM cells from a primary human biopsy (P3), were used in vitro and in vivo to evaluate the efficacy of TFP treatment. Viability and cytotoxicity was evaluated by CCK-8 and clonogenic formation assays. Molecular studies using immunohistochemistry, western blots, immunofluorescence and qPCR were used to gain mechanistic insight into the biological activity of TFP. Preclinical therapeutic efficacy was evaluated in orthotopic xenograft mouse models. Results IC50 values of U251, U87 and P3 cells treated with TFP were 16, 15 and 15.5 ...
Microbiome interactions are important determinants for ecosystem functioning, stability, and health. In previous studies, it was often observed that bacteria suppress potentially pathogenic fungal species that are part of the same plant microbiota; however, the underlying microbe-microbe interplay remains mostly elusive. Here, we explored antagonistic interactions of the fungus Fusarium graminearum and bacterium Streptomyces hygroscopicus at the molecular level. Both are ubiquitous members of the healthy wheat microbiota; under dysbiosis, the fungus causes devastating diseases. In co-cultures, we found that Streptomyces alters the fungal acetylome leading to substantial induction of fungal autophagy. The bacterium secrets rapamycin to inactivate the target of rapamycin (TOR), which subsequently promotes the degradation of the fungal histone acetyltransferase Gcn5 through the 26S proteasome. Gcn5 negatively regulates fungal autophagy by acetylating the autophagy-related protein Atg8 at the lysine site
Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe. 2012 Apr 19; 11(4):397-409 ...
TY - JOUR. T1 - Chloroplasts are partially mobilized to the vacuole by autophagy. AU - Ishida, Hiroyuki. AU - Yoshimoto, Kohki. PY - 2008/10/1. Y1 - 2008/10/1. N2 - Excluding the central vacuole, chloroplasts constitute the largest compartment within the leaf cells of plants and contain approximately 80 percent of the total leaf nitrogen, mainly as proteins. Much of this nitrogen is allocated to the carbon-fixing enzyme in photosynthesis, Rubisco. During senescence, plants can mobilize nitrogen from chloroplasts in older leaves to other organs, such as developing seeds. Whereas bulk degradation of the cytosol and organelles in plants occurs by autophagy, the role of autophagy in the degradation of chloroplast proteins is still unclear. We have recently demonstrated that stroma-targeted green fluorescent protein (GFP), DsRed, and GFP-labeled Rubisco can be mobilized to the vacuole of living cells via Rubisco-containing bodies, in an ATG gene-dependent manner. Our results indicate the presence of ...
Cuervo, Ana Maria; Bergamini, Ettore; Brunk, Ulf T; Dröge, Wulf; Ffrench, Martine; Terman, Alexei (2005). "Autophagy and Aging ... the Importance of Maintaining "Clean" Cells". Autophagy. 1 (3): 131-40. doi:10.4161/auto.1.3.2017. PMID 16874025.. ... has been shown to up-regulate autophagy, the repair mechanism of the cell.[26] A related hypothesis suggests that caloric ... restriction works by decreasing insulin levels and thereby up-regulating autophagy,[26][27] but caloric restriction affects ...
"Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease". Autophagy. 11 (9): 1443-57. doi ...
"Staphylococcus aureus promotes autophagy by decreasing intracellular cAMP levels". Autophagy. 8 (12): 1865-7. doi:10.4161/auto ...
"Autophagy. 4 (2): 141-50. doi:10.4161/auto.5190. PMID 17986870.. *. Vashist S, Ng DT (April 2004). "Misfolded proteins are ...
autophagy. • positive regulation of transcription, DNA-templated. • embryonic placenta development. • lysosome organization. • ... positive regulation of autophagy. • positive regulation of transcription from RNA polymerase II promoter. • immune system ... "MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB". Autophagy. 8 (6): 903- ... "RRAG GTPases link nutrient availability to gene expression, autophagy and lysosomal biogenesis". Autophagy. 9 (6): 928-30. doi ...
Kern A, Dikic I, Behl C (2015). "The integration of autophagy and cellular trafficking pathways via RAB GAPs". Autophagy. 11 ( ... Autophagy (from Greek words for "self" and "eating") is a process of digesting or degrading cytoplasmic molecules (proteins, ... Kim BW, Kwon DH, Song HK (2016). "Structure biology of selective autophagy receptors". BMB Reports. 49 (2): 73-80. doi:10.5483/ ... Kruppa AJ, Kendrick-Jones J, Buss F (2016). "Myosins, Actin and Autophagy". Traffic (Copenhagen, Denmark). 17 (8): 878-90. doi: ...
His original findings about autophagy in yeast cells:[17] *. Ohsumi, Yoshinori; et al. (October 1992). "Autophagy in Yeast ... Yoshinori Ohsumi (大隅 良典, Ōsumi Yoshinori, born February 9, 1945) is a Japanese cell biologist specializing in autophagy, the ... In 2016, he was awarded the Nobel Prize in Physiology or Medicine "for his discoveries of mechanisms for autophagy".[9][10] He ... "Yoshinori Ohsumi wins Nobel prize in medicine for work on autophagy". The Guardian. Retrieved 3 October 2016.. ...
Autophagy. 6 (4): 506-22. doi:10.4161/auto.6.4.11863. PMID 20505359. Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The ... "Membrane trafficking events that partake in autophagy". Curr Opin Cell Biol. 22 (2): 150-6. doi:10.1016/j.ceb.2009.11.013. PMID ... is aberrantly expressed in human cancer and is linked to starvation-induced autophagy". Oncogene. 23 (58): 9314-25. doi:10.1038 ... The Atg proteins regulate autophagy, which is a lysosomal degradation pathway required for maintaining cell health, surviving ...
Xie W, Zhang L, Jiao H, Guan L, Zha J, Li X, Wu M, Wang Z, Han J, You H (Jul 2015). "Chaperone-mediated autophagy prevents ... Hsc70 is known to localize to the cytoplasm and lysosome, where it participates in chaperone-mediated autophagy by aiding the ... Hsc70 is a key component of chaperone-mediated autophagy wherein it imparts selectivity to the proteins being degraded by this ... Majeski AE, Dice JF (2004). "Mechanisms of chaperone-mediated autophagy". Int. J. Biochem. Cell Biol. 36 (12): 2435-44. doi: ...
... inhibitors cause cell death also in A-375 melanoma cells, which depend on autophagy for growth and proliferation, due ... February 2019). "A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt ... February 2019). "A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt ... multiple events in lysosome homeostasis". Autophagy. 15 (10): 1694-1718. doi:10.1080/15548627.2019.1586257. PMC 6735543. PMID ...
... elegans screen identifies autophagy genes specific to multicellular organisms". Cell. 141 (6): 1042-55. doi:10.1016/j.cell. ... but unlike macroautophagy and chaperone-mediated autophagy, it is mediated-in mammals by lysosomal action or in plants and ...
Autophagy. 15 (12): 2167-2168. doi:10.1080/15548627.2019.1666595. PMC 6844521. PMID 31512558. Laraia L, Friese A, Corkery DP, ...
"RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy". Autophagy. 10 (12): 2297-2309. doi:10.4161/15548627.2014 ... Further, the RAB3GAP1 knockdown has shown to affect the autophagy and mineralization potential of human primary osteoblasts. ... RAB3GAP is reported to modulate basal and rapamycin-induced autophagy in human fibroblasts and C. elegans. ... "Estrogen enhances human osteoblast survival and function via promotion of autophagy". Biochimica et Biophysica Acta (BBA) - ...
Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the ... Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is ... "Entrez Gene: Autophagy related 4D, cysteine peptidase". Betin VM, MacVicar TD, Parsons SF, Anstee DJ, Lane JD (April 2012). "A ... This gene belongs to the autophagy-related protein 4 (Atg4) family of C54 endopeptidases. Members of this family encode ...
229-32 Martin, S J (August 2011). "Oncogene-induced autophagy and the Goldilocks principle". Autophagy. 7 (8): 922-3. doi: ...
... , FMedSci is an American cell biologist who has made significant contributions to the Autophagy field. She is a ... Since then her lab has identified several mammalian Atg proteins and continues to contribute to understanding of autophagy at ... Tooze is an affiliate member of the Autophagy Inflammation and Metabolism Centre of Biomedical Research Excellence. In 2018, ... "Affiliates and Council Members , Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence". www. ...
Pandey UB, Batlevi Y, Baehrecke EH, Taylor JP (Nov-Dec 2007). "HDAC6 at the intersection of autophagy, the ubiquitin-proteasome ... "HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS". Nature. 447 (7146): 859-63. ... system and neurodegeneration". Autophagy. 3 (6): 643-5. doi:10.4161/auto.5050. PMID 17912024. Pandey UB, Nie Z, Batlevi Y, ...
2016). "AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects". Autophagy. 12 (2): ... AUTEN-67 is an autophagy-enhancing drug candidate that increases autophagic flux in cell lines and in vivo models. It hampers ... May 2016). "AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of ...
Autophagy. 2018; 14(10). Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation ...
"MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins". Autophagy. 8 (12): 1724-40. doi:10.4161/auto. ... in a process that stimulates autophagy. A number of additional proteins also interact with MAPK15, including cyclin-dependent ...
October 2014). "FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation". Autophagy ... Additional potential roles for FLCN in autophagy, TGF β signaling, regulation of AMPK activity, and regulation of HIF-1α ... "Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy". PLOS ONE. 8 (7): ... "Folliculin regulates ampk-dependent autophagy and metabolic stress survival". PLOS Genetics. 10 (4): e1004273. doi:10.1371/ ...
Autophagy is induced upon nutrient depletion or rapamycin treatment and leads to the response of more than 30 autophagy-related ... Autophagy. 1 (2): 119-26. doi:10.4161/auto.1.2.1859. PMID 16874047. Ohsumi Y (March 2001). "Molecular dissection of autophagy: ... autophagy autophagin ATG5 ATG7 ATG12 MAP1LC3A GABARAP PDB: 1UGM​; Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, ... After starvation autophagy is induced through the activation of Atg proteins both on the protein modification and the ...
Work with yeast pex6 mutants has shown that PEX6 is a key player in the autophagy of peroxisomes called pexophagy. Mutations in ... Autophagy. 10 (5): 835-45. doi:10.4161/auto.28259. PMC 5119063. PMID 24657987. Waterham HR, Ebberink MS (September 2012). " ...
Autophagy. 7 (10): 1098-107. doi:10.4161/auto.7.10.15904. PMID 21597319. Rozenknop A, Rogov VV, Rogova NY, Löhr F, Güntert P, ...
Autophagy. Researching how autophagy-a process by which cells eliminate abnormal proteins-can help prevent the destruction of ...
Klionsky DJ (August 2008). "Autophagy revisited: a conversation with Christian de Duve". Autophagy. 4 (6): 740-3. doi:10.4161/ ... He LQ, Lu JH, Yue ZY (May 2013). "Autophagy in ageing and ageing-associated diseases". Acta Pharmacologica Sinica. 34 (5): 605- ... Lieberman AP, Puertollano R, Raben N, Slaugenhaupt S, Walkley SU, Ballabio A (May 2012). "Autophagy in lysosomal storage ... Moriyasu Y, Ohsumi Y (August 1996). "Autophagy in Tobacco Suspension-Cultured Cells in Response to Sucrose Starvation". Plant ...
... is involved in chaperone-assisted selective autophagy. BAG proteins compete with Hip-1 for binding to the Hsc70/Hsp70 ... This process is called chaperone-assisted selective autophagy and is essential for maintaining muscle activity in flies, mice ... Autophagy. 4 (2): 237-9. doi:10.4161/auto.5407. PMID 18094623. "Entrez Gene: BAG3 BCL2-associated athanogene 3". Arndt V, Dick ... "Chaperone-assisted selective autophagy is essential for muscle maintenance". Current Biology. 20 (2): 143-8. doi:10.1016/j.cub. ...
Likewise, inhibition of PFKFB3 has been found to induce autophagy. See summary image. Autophagy can prolong cellular survival ... It was found that RA T cell fail to upregulate autophagy, and knockout experiments placed PFKFB3 as an upstream regulator of ... 3PO decreases glucose uptake and increases autophagy. Research is currently exploring various 3PO derivatives (i.e. PFKF15) in ... Enhanced activity of PFKFB3 accelerates ROS production as an end product of glycolysis, and thus increases autophagy. ...
This relationship between autophagy and BNIP3 is widely supported in many studies. In ceramide- and arsenic trioxide- treated ... Zhang J, Ney PA (July 2009). "Role of BNIP3 and NIX in cell death, autophagy, and mitophagy". Cell Death and Differentiation. ... Kroemer and Levine believe that this name is a misnomer because cell death usually occurs with autophagy rather than by ... Its deletion results in the inability to induce autophagy. Once integrated in the OMM, BNIP3 exists as an inactive monomer ...
Autophagy is executed by autophagy-related (Atg) genes. The first autophagy genes were identified by genetic screens conducted ... "Autophagy in Stress, Development & Disease, 2003, Gordon Research Conference".. *^ "Autophagy in Health and Disease (Z3), 2007 ... Negative regulators of autophagy[edit]. Negative regulators of autophagy, such as mTOR, cFLIP, and EGFR are orchestrated to ... relationship between cancer and autophagy continues to be a main theme of autophagy research. The roles of autophagy in ...
Autophagy is executed by autophagy-related (Atg) genes. The first autophagy genes were identified by genetic screens conducted ... "Autophagy in Stress, Development & Disease, 2003, Gordon Research Conference".. *^ "Autophagy in Health and Disease (Z3), 2007 ... In the selective autophagy is the autophagy of oragenelles; mitophagy,[30] lipophagy,[31] pexophagy,[32] chlorophagy,[33] ... Negative regulators of autophagy[edit]. Negative regulators of autophagy, such as mTOR, cFLIP, and EGFR are orchestrated to ...
Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a ... Autophagy promotes lipid hydrolysis and generation of free fatty acids by releasing the content of lipid droplets to lysosomes ... This work identifies a critical role of autophagy in regulating lipid metabolism and may provide a new approach to the ... A critical role of autophagy in regulating lipid metabolism is identified, and may provide a new approach to prevent lipid ...
The process of autophagy has been conserved over time among all living organisms. The process is similar in single cellular ... Autophagy is induced when the cell is put under stress or there is depletion of growth factors and/or nutrients in the media ... The process of autophagy has been conserved over time among all living organisms. The process is similar in single cellular ... As the signals for autophagy are in place and there is induction of the process, the next step is to select the material that ...
When there is starvation or nutrient deprivation, the process of autophagy is triggered. This gives rise to formation of double ... Autophagy plays an important role in the survival of cellular organisms. ... Autophagy and cell death. There is an association between cell death and autophagy. There is also a link between programmed ... Autophagy and cellular survival. Autophagy plays an important role in the survival of cellular organisms. When there is ...
... there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy ... Current autophagy-modulating compounds in clinical trials are also summarized. ... Since the discovery of autophagy-related (Atg) genes in the 1990s, ... Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. ...
A lot more work is needed in order for us to really understand how mutations in LRRK2 alter autophagy, but this study provides ... Public lecture: The autophagy signaling network, c--‐myc and pathology: dont mess with the cell cycle! ... suggesting that there may be changes in the way that these cells regulate a key process called autophagy (a term which comes ... seem to have a similar impact on autophagy. This is important because, up until now, there hasnt been a clear cellular symptom ...
Autophagy is the major cellular pathway to degrade dysfunctional organelles and protein aggregates. Autophagy is particularly ... as well as the cell biology of bulk and selective autophagy in neurons. Finally, we discuss the role of autophagy in neuronal ... Autophagy in Neurons.. Stavoe AKH1, Holzbaur ELF1.. Author information. 1. Department of Physiology, University of Pennsylvania ... There are both constitutive and stress-induced pathways for autophagy in neurons, which catalyze the turnover of aged or ...
Autophagy, as a highly conserved cellular process, can achieve the degradation and recycling of intracellular substances, and ... Autophagy in stem cells. Autophagy. 2013;9(6):830-49.CrossRefPubMedPubMedCentralGoogle Scholar ... Autophagy revisited: a conversation with Christian de Duve. Autophagy. 2008;4(6):740-3.CrossRefPubMedGoogle Scholar ... Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Autophagy. 2010;107( ...
Autophagy is recognized as the main tool to degrade damaged organelles and misfolded proteins. Slideshow includes: Autophagic ... Autophagy Research Focus by Proteintech * 1. 1Cardiovascular Research Focus www.ptglab.com AUTOPHAGY RESEARCH FOCUS www.ptglab. ... Autophagy is recognized as the main tool to degrade damaged organelles and misfolded proteins. Slideshow includes: Autophagic ... 4. 4Cardiovascular Research Focus www.ptglab.com BECLIN 1 ANTIBODY A core component of the autophagy machinery -- Antibody Name ...
Autophagy and aging.. Rubinsztein DC1, Mariño G, Kroemer G.. Author information. 1. Department of Medical Genetics, University ... Genetic inhibition of autophagy induces degenerative changes in mammalian tissues that resemble those associated with aging, ... Here, we discuss the probable cause and effect relationship between perturbed autophagy and aging, as well as possible ... Pharmacological or genetic manipulations that increase life span in model organisms often stimulate autophagy, and its ...
Postdoc positions in our group are available to (1) study molecular mechanisms of selective autophagy; (2) determine the role ... identify small molecules that target selective autophagy. - Ph.D. or M.D./Ph.D. in immunology, cell biology or molecular ... and to develop successful strategies to increase autophagy in cells, thereby leading to new strategies to treat infectious ... of novel autophagy genes in antibacterial defenses in vivo and identify cell-specific functions of those genes; and (3) ...
Background Autophagy is a specific universal biological phenomenon in eukaryotic cells, which is characterized by cytoplasmic ... Mizushima N (2007) Autophagy: process and function. Genes Dev 21(22):2861-2873PubMedCrossRefGoogle Scholar ... Reggiori F, klionsky DJ (2002) Autophagy in the eukaryotic cell. Eukaryot Cell 1(1):11-21PubMedCentralPubMedCrossRefGoogle ... Autophagy Hippocampal neurons Alzheimers disease (AD) Hypoxia-ischemia Excitotoxicity Vitamin E This is a preview of ...
On page 878 of this issue, Goginashvili et al. (4) show how β cells avoid inappropriate autophagy, and describe a form of this ... This process of autophagy (2), however, poses a problem for the bodys specialized fuel-sensing cells. β cells within the ... autophagy under basal conditions could compromise the ability to respond optimally to fluctuations in blood glucose, posing a ...
6. Autophagy, Associates in Crime?. Not only can autophagy act as an energy fueler for HSCs activation, it can as well induce ... Autophagy induces the activation of HSCs, a key process for the genesis of hepatic fibrosis. In addition, autophagy plays ... Inhibition of autophagy with 3-methyladenine (3-MA) markedly inhibited the production of HBV [77]. HBV induced autophagy is ... S. Jin and E. White, "Role of autophagy in cancer: management of metabolic stress," Autophagy, vol. 3, no. 1, pp. 28-31, 2007. ...
Autophagy * Pharmacologic agents targeting autophagy Helin Vakifahmetoglu-Norberg et al. * Development of autophagy inducers in ... Induction of autophagy decreases tau levels (22, 23). In contrast, loss of autophagy by conditional knockout of the autophagy ... autophagy is required for maintenance of axonal homeostasis, and loss of autophagy results in axonal dystrophy (4). Autophagy ... Immunologic manifestations of autophagy Vojo Deretic et al. * Essential role for autophagy in life span extension Frank Madeo ...
Autophagy and Cancer. Editors. * Hong-Gang Wang Series Title. Current Cancer Research. Copyright. 2013. Publisher. Springer- ... With the explosion of information on autophagy in cancer, this is an opportune time to speed the efforts to translate our ... This book will cover the latest advances in this area from the basics, such as the molecular machinery for autophagy induction ... The remaining chapters will cover topics on autophagy and cancer therapy. These pages will serve as a description on how the ...
... Guest Editors: Arkadiusz Orzechowski, Saverio Bettuzzi, Patrycja Pawlikowska, and Beata Pająk * ... Roles of Autophagy Induced by Natural Compounds in Prostate Cancer, V. Naponelli, A. Modernelli, S. Bettuzzi, and F. Rizzi ... The Importance of Autophagy Regulation in Breast Cancer Development and Treatment, Joanna Magdalena Zarzynska Review Article (9 ... Control of Autophagy in Cancer, Arkadiusz Orzechowski, Saverio Bettuzzi, Patrycja Pawlikowska, and Beata Pająk Editorial (2 ...
... comprises several evolutionarily conserved mechanisms for uptake and transport of proteins and even cytoplasmic ... Autophagy is carried out by a set of more than 30 proteins encoded by the Autophagy‐Related genes (ATGs), the functions of ... Autophagy 10: 1154-1166.. Ward C, Martinez‐Lopez N, Otten EG, et al. (2016) Autophagy, lippophagy and lysosomal storage ... Jain N and Ganesh S (2016) Emerging nexus between RAB GTPases, autophagy and neurodegeneration. Autophagy 12: 900-904. ...
Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other ... Autophagy in Immunity Against Mycobacterium tuberculosis: a Model System to Dissect Immunological Roles of Autophagy ... An immunological role of autophagy was first recognized with the discovery of autophagys ability to sanitize the cellular ... Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it ...
This entry represents autophagy protein 16 (Apg16), which is required for the function of the Apg12p-Apg5p conjugate. ... Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway.. EMBO J. 18 3888-96 1999 ... During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Auotphagy protein ... Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting ...
Autophagy in mammalian systems by Daniel J. Klionsky; 1 edition; First published in 2009; Subjects: Autophagic vacuoles, ... Biochemistry, Apoptosis, Cellular control mechanisms, Eukaryotic cells, Life Sciences, Autophagy, SCIENCE, Eukaryotic Cells, ... Autophagy in mammalian systems edited by Daniel J. Klionsky Published 2009 by Academic in San Diego, Calif, London . Written in ... Methods for monitoring autophagy Using GFP-LC3 transgenic mice / Noboru Mizushima. Using photoactivatable proteins to monitor ...
UMass Medical School researcher Eric Baehrecke has identified a protein in Drosophila that plays an essential role in autophagy ... Autophagy is the process cells use to degrade used or damaged components inside the cell for recycling. Normally autophagy acts ... Communication between neighboring cells triggers autophagy. Breakdown of a link between immune response and autophagy may ... "Autophagy, a natural and highly regulated degradation process, appears to be influenced by systemic, body-wide signals, such as ...
... Curr Biol. 2017 Apr 24;27(8):R318-R326. doi: 10.1016/j.cub.2017.02.061. ... we highlight the considerable progress made recently towards understanding the diverse roles of the cytoskeleton in autophagy. ...
Autophagy is responsible for the degradation of most long-lived proteins and some organelles. Cytoplasmic constituents, ... Autophagy is an intracellular bulk degradation system that is found ubiquitously in eukaryotes. ... Autophagy is an intracellular bulk degradation system that is found ubiquitously in eukaryotes. Autophagy is responsible for ... Methods for monitoring autophagy Int J Biochem Cell Biol. 2004 Dec;36(12):2491-502. doi: 10.1016/j.biocel.2004.02.005. ...
Autophagy may be the key to finding treatments for early Huntingtons disease Autophagy disruption may be at the root of early ... Recent evidence indicates that autophagy plays a central role in synaptic maintenance, and the disruption in autophagy may be ... "Autophagy plays a specialized role in the maintenance and function of the synapse, and mHtt may disrupt this function, leading ... "We have long thought that autophagy played a role in the pathophysiology of HD, but what this role is has been unclear until ...
GTPases in Trafficking, Autophagy and Disease. Federation of American Societies for Experimental Biology ... Autophagy, Rag GTPases, and GTPases and disease. The sessions will include 30 regular talks and at least 12 short talks ... Autophagy and Disease". Represented disciplines will include biochemists, structural biologists, membrane biologists, cell ...
Autophagy may refer to: Autophagy (cellular process), a process in cellular biology Autophagia, a mental disorder or a symptom ... a scientific journal Self-cannibalism This disambiguation page lists articles associated with the title Autophagy. If an ...
When the autophagy protein Atg7 is absent, nutrient withdrawal does not stop the cell cycle. ... When the autophagy protein Atg7 is absent, nutrient withdrawal does not stop the cell cycle. ... Starvation stimulates withdrawal from the cell cycle, as well as stimulating autophagy. Are these two events connected? Lee et ... show a direct and nutrient-sensitive interaction between the tumor suppressor p53 and the essential autophagy gene Atg7. ...
  • Autophagy is the major cellular pathway to degrade dysfunctional organelles and protein aggregates. (nih.gov)
  • Here we review the core components of the pathway for autophagosome biogenesis, as well as the cell biology of bulk and selective autophagy in neurons. (nih.gov)
  • Klionsky DJ, Emr SD (2000) Autophagy as a regulated pathway of cellular degradation. (springer.com)
  • PI3K/Akt/mTOR signaling pathway is a major contributor for autophagy. (hindawi.com)
  • The pathway for major molecular steps in autophagy. (els.net)
  • Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway [ PMID: 10712513 ]. (ebi.ac.uk)
  • Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. (ebi.ac.uk)
  • image: Proposed pathway of mutant huntingtin (mHtt) contribution to cognitive dysfunction and cell death through impairments in synaptic autophagy: the Huntingtin protein (mHtt) interferes with autophagic efficiency, leading to a decline in synaptic autophagy. (eurekalert.org)
  • Next, they review the growing evidence that the lysosome-mediated degradation pathway autophagy plays a central role in synaptic maintenance, and how the disruption in autophagy may contribute to early cognitive changes in HD. (eurekalert.org)
  • Although initially characterised as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells. (wikipedia.org)
  • This pathway highlights the triggers of autophagy, such as hypoxia or nutrient starvation and how autophagy helps maintain cell homeostasis. (abcam.com)
  • Download our Autophagy in heart disease pathway. (abcam.com)
  • Collectively, the current data reveal that autophagy suppresses light-dependent retinal degeneration in collaboration with the endosomal degradation pathway and that rhodopsin is a key substrate for autophagic degradation in this context. (mendeley.com)
  • We have collected recent evidence implicating autophagy, a highly conserved pathway for recycling intracellular proteins and organelles, in the pressure-stressed heart. (utsouthwestern.edu)
  • Autophagy is a major cellular metabolic pathway that facilitates degradation of a subset of long-lived proteins and cytoplasmic organelles in eukaryotic cells. (royalsocietypublishing.org)
  • In LAP, elements of the autophagy pathway conjugate LC3 to phagosomes, which contain engulfed particles, including dying cells. (royalsocietypublishing.org)
  • Autophagy is a major intracellular pathway in the delivery of cytoplasmic material to lysosomes for degradation. (uniprot.org)
  • Autophagy, a lysosomal degradation pathway, plays a crucial role in removing protein aggregates as well as damaged organelles to maintain intracellular homeostasis during various stress conditions ( 8 , 9 ) that are involved in the pathogenesis of diabetic nephropathy. (diabetesjournals.org)
  • Chlorogenic acid alleviates autophagy and insulin resistance by suppressing JNK pathway in a rat model of nonalcoholic fatty liver disease. (greenmedinfo.com)
  • The tuberous sclerosis complex-Ras homologue enriched in brain-mammalian target of rapamycin (TSC-Rheb-mTOR) pathway is known to play a central role in modulating protein synthesis and autophagy. (pnas.org)
  • At present, no one has tried to link autophagy to the sir-2 pathway, although Levine admits that she's pondered the notion. (fightaging.org)
  • When the genes for autophagy in cells are disabled, the longevity enhancing effects of spermidine go away, which reinforces its role in this important pathway. (abovetopsecret.com)
  • Although in most mammalian cells autophagy occurs at basal levels, stress or starvation strongly upregulate this pathway ( 4 ). (diabetesjournals.org)
  • Autophagy primitively portrayed as an evolutionarily conserved process is involved in cellular homeostasis by facilitating the lysosomal degradation pathway for the recycling and elimination of intracellular defective macromolecules and organelles. (intechopen.com)
  • The process and regulation of macroautophagy, which is the primary and most studied autophagy pathway, is depicted in the figure below. (biolegend.com)
  • Autophagy is an essential degradative pathway that maintains neuronal homeostasis and prevents axon degeneration. (jneurosci.org)
  • By identifying key components of this broadly conserved membrane traffic pathway, yeast geneticists generated tools for microbiologists and immunologists to explore whether autophagy contributes to host defenses. (jimmunol.org)
  • Mounting evidence also indicates that autophagy equips cells to deliver cytosolic Ags to the MHC class II pathway. (jimmunol.org)
  • By applying knowledge of the autophagy machinery and exploiting microbes as genetic probes, experimentalists can now examine in detail how this ancient membrane traffic pathway contributes to these and other mechanisms critical for infection and immunity. (jimmunol.org)
  • The autophagy pathway engulfs and degrades a variety of bacteria that invade the cytoplasm (Table I ⇓ ), establishing its credentials as a component of innate immunity. (jimmunol.org)
  • For example, Schlossmacher reported that levels of a key autophagy marker drop in immune cells containing mutant LRRK2, suggesting this pathway is impaired. (alzforum.org)
  • Autophagy is a survival pathway wherein non-functional proteins and organelles are degraded in lysosomes for recycling and energy production. (scielo.br)
  • Autophagy is a process of cellular self-degradation and is a major pathway for elimination of cytoplasmic material by the lysosomes. (mdpi.com)
  • researchers have "shown that autophagy, a pathway preserved during evolution, functions to engulf and digest cholesterol accumulated in artery walls. (fightaging.org)
  • The autophagy pathway, which means self-digestion, developed early in single-cell organisms to allow the clearance of accumulated dysfunctional molecules. (fightaging.org)
  • The finding that autophagy also functions to digest and liberate cholesterol from cells and the fact that we know this pathway is regulated offers hope for the development of new drugs that could activate export of cholesterol from the walls of arteries. (fightaging.org)
  • Upon starvation cells undergo autophagy, a cellular degradation pathway important in the turnover of whole organelles and long lived proteins. (mcponline.org)
  • Autophagy is considered as an unselective bulk degradation pathway. (mcponline.org)
  • Dysregulation of autophagy or mutations in proteins involved in this pathway have been shown to contribute to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. (biolegend.com)
  • We compared the effect of short- and long-established steatosis on the intensity of autophagy-lysosomal pathway in rat liver A commonly used approach to monitor and analyze autophagy flux is via blockade of autophagic activity. (musicaenlamochila.net)
  • we performed an autophagy flux assay using CQ, which prevents fusion between autophagosomes and lysosomes (Fig. Overexpression of a dominant negative form of Atg5 increased paraquat- and MPP + -induced cell death Autophagy autophagy flux chloroquine modulation, through rapamycin or chloroquine, induced a reduction of cell proliferation (Figure 4(c)), confirming that autophagy is a finely controlled pathway. (musicaenlamochila.net)
  • Further exploration of the possible mechanisms of MOF-induced autophagy revealed that the inhibition of mTOR pathway as well as the enhancement of Becline1 and Atg5 contributed to autophagy induction. (rsc.org)
  • Based on the pathway via which cargo marked for degradation is delivered to the lysosome, three types of autophagy have been described ( Figure 1 ). (sigmaaldrich.com)
  • The third type of autophagy is known as macroautophagy, which it is the major autophagy pathway in mammalian cells. (sigmaaldrich.com)
  • The Atg proteins regulate autophagy, which is a lysosomal degradation pathway required for maintaining cell health, surviving periods of nutrient deprivation and also plays a role in cancer, neurodegeneration and immune responses to a diverse range of pathogens. (wikipedia.org)
  • Autophagy allows the orderly degradation and recycling of cellular components. (wikipedia.org)
  • A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. (nature.com)
  • Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. (nature.com)
  • Autophagy, as a highly conserved cellular process, can achieve the degradation and recycling of intracellular substances, and is crucial for maintaining cellular homeostasis and remodeling of normal development. (springer.com)
  • 3. 3Cardiovascular Research Focus www.ptglab.com AUTOPHAGIC DEGRADATION Figure 1: Macroautophagy, microautophagy, and chaperone-mediated autophagy play main roles in the lysosomal degradation pathways in mammalian cells. (slideshare.net)
  • Autophagy comprises several evolutionarily conserved mechanisms for uptake and transport of proteins and even cytoplasmic organelles to the lysosome for degradation. (els.net)
  • Autophagy is a process in which a cup‐shaped, double‐membrane phagophore develops from a region of or near modified endoplasmic reticulum and closes, either unselectively in bulk or selectively, around sequestered cytoplasmic cargos, finally fusing with a lysosome to deliver the contents for degradation. (els.net)
  • An immune-related protein deployed between neighboring cells in Drosophila plays an essential role in the cell-degradation process known as autophagy, according to new research by Eric H. Baehrecke, PhD, at UMass Medical School. (umassmed.edu)
  • Using the development of the salivary gland in Drosophila, which degrades as flies mature, to isolate and study the components of autophagy, Baehrecke theorized that a rise in a protein called Mcr in the glands prior to cell death was somehow connected to its degradation. (umassmed.edu)
  • Autophagy is an intracellular bulk degradation system that is found ubiquitously in eukaryotes. (nih.gov)
  • Autophagy is responsible for the degradation of most long-lived proteins and some organelles. (nih.gov)
  • Autophagy is a cellular process that isolates cytoplasmic components that can be directed to the lysosome for degradation. (abcam.com)
  • Autophagy involves a series of sequential steps that start with initiation/sequestration, continue with fusion with lysosomes, ultimately leading to degradation. (abcam.com)
  • Autophagy-mediated degradation of specific proteins and organelles can occur via targeting proteins. (abcam.com)
  • Autophagy sees a cell destroy its own contents by enclosing it in membranes, forming sack-like vesicles that had been transported to a recycling compartment, called the lysosome, for degradation. (siliconrepublic.com)
  • Autophagy is a tightly regulated process that facilitates degradation of overabundant or malfunctioning cellular components, including damaged organelles, misfolded proteins, invasive microorganisms and cells themselves [ 1 , 2 ]. (royalsocietypublishing.org)
  • Professor Christian Behl said, "The controlled protein degradation by autophagy is a core aspect of protein homoeostasis, which means the complex interplay between the formation, folding, and decomposition of proteins. (medindia.net)
  • Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. (mdpi.com)
  • Autophagy can also involve the degradation of damaged or aged organelles, and misfolded or damaged proteins to eliminate these components that might otherwise be deleterious to cellular survival. (mdpi.com)
  • For instance, blockage of autophagy and autophagolysosomal degradation in mice using genetic tools resulted in hepatosteatosis and hepatomegaly (9). (thefreelibrary.com)
  • Autophagy is required for the degradation of damaged organelles and long-lived proteins, as well as for the development of glands such as the breast and prostate. (wellnessresources.com)
  • The study, published in the February 1 issue of Cancer Research, found that deletion of the Sirt1 gene in mice resulted in PIN lesion formation associated with reduced autophagy, which is the necessary degradation of a cell's own components and most likely essential for tumor suppression. (wellnessresources.com)
  • Autophagy is an intracellular degradation process in which cytoplasmic components, including organelles, are directed to the lysosome by a membrane-mediated process ( 3 ). (pnas.org)
  • Cells mainly deploy 3 mechanisms to counteract misfolded proteins: up-regulating chaperones to assist protein refolding ( 1 ), proteolytic degradation of the misfolded/damaged proteins involving ubiquitin-proteasome and autophagy-lysosome systems ( 2 ), and formation of detergent-insoluble aggresome by transporting the misfolded proteins to the juxtanuclear region in a microtubule-dependent manner ( 3 , 4 ). (pnas.org)
  • Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to lysosomes ( 15 , 16 ). (pnas.org)
  • Consistent with the inhibitory role of mTORC1 in autophagy regulation ( 15 , 16 ), the TSC1 −/− mouse embryonic fibroblast (MEF), which has high mTORC1 activity ( 20 ), displayed a lower basal conversion of the autophagy marker LC3-I to LC3-II than the TSC1 +/+ MEF ( Fig. 1 A ). One would predict that the TSC1 −/− MEFs should accumulate more aggresomes when proteasome degradation is inhibited. (pnas.org)
  • In cell biology , autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. (fightaging.org)
  • I believe that the induction of autophagy in caloric restriction-or loss-of-function mutation in insulin signaling -leads to increased degradation of damaged mitochondria and reduction of oxidative stress ," says Levine. (fightaging.org)
  • Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein that binds LC3/Atg8, thereby promoting autophagy by bringing SQSTM1-containing protein aggregates to the autophagosome for degradation. (cellsignal.com)
  • Many other autophagy proteins are then involved in the downstream process of creating and elongating the phagophore (2), joining the phagophore ends to complete the phagosome around cytoplasmic contents (3), and finally fusing the phagosome with the lysosome for degradation (4). (biolegend.com)
  • Rather, constitutive autophagy in neurons may function to maintain cellular homeostasis by balancing synthesis and degradation, especially within distal axonal processes far removed from the soma. (jneurosci.org)
  • Another special property illustrated in Fig. 1 is that autophagy acts as a topological inverter-bringing molecules and objects from the cytosolic side to the luminal side for degradation or processing, interaction with luminal receptors, or secretion from cells. (jimmunol.org)
  • Autophagy enables eukaryotic cells to capture cytoplasmic components for degradation within lysosomes. (jimmunol.org)
  • Researchers at the University of Massachusetts Medical School, gained new insights into autophagy -- a cellular degradation process associated with a form of programmed cell death -- by studying the salivary gland cells of the fruit fly. (science20.com)
  • In "Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila," published in the December 14 issue of Cell, Eric Baehrecke, PhD, UMMS Associate Professor of Cancer Biology, and colleagues examined fly salivary glands, which contain all of the machinery required to dismantle and recycle their own cellular components and thus provide a genetic model system for elucidating the complex functions of autophagy. (science20.com)
  • Autophagy is responsible for the degradation of damaged organelles and protein aggregates and therefore plays a significant role in cellular homeostasis. (mdpi.com)
  • Despite the initial belief that autophagy is a nonselective bulk process, there is growing evidence during the last years that sequestration and degradation of cellular material by autophagy can be accomplished in a selective and specific manner. (mdpi.com)
  • Thus, starvation induces degradation via autophagy, which appears to be selective and to degrade proteins in an ordered fashion and not completely arbitrarily as anticipated so far. (mcponline.org)
  • Autophagy is responsible for cytoplasmic bulk degradation and thought to be important for the turnover of whole organelles and long lived proteins ( 8 , 9 ). (mcponline.org)
  • However, lately selective types of autophagy have been described that lead to the elimination of specific organelles or protein aggregates ( 17 ), such as ER-phagy for ER-specific degradation ( 18 ), mitophagy for mitochondria-specific degradation ( 19 ), and ribophagy for ribosome-specific degradation ( 20 ). (mcponline.org)
  • Autophagy is a non-selective and bulk intracellular degradation system of eukaryotic cells and is highly conserved from yeast to human. (genome.jp)
  • Autophagy is a regulated process for protein degradation and turnover of damaged organelles to maintain cellular homeostasis. (biolegend.com)
  • Autophagy is the lysosomal-dependent degradation process of intracellular substances in adaptation to environmental or developmental changes. (rsc.org)
  • Upon the induction of selective autophagy, proteins prone for degradation are initially gathered around the cell nucleus. (innovations-report.com)
  • Less research has been done on the interplay of autophagy with other mechanisms, such as the intake of substrates by the invagination of the cell membrane (endocytosis), programmed cell death (apoptosis), and the ubiquitin system, which marks proteins for degradation by the proteasome. (innovations-report.com)
  • Autophagy describes the segregation and delivery of cytoplasmic cargo, including proteins and organelles, for degradation by hydrolytic enzymes through the lysosomal machinery. (thermofisher.com)
  • Listeria lacking ActA becomes rapidly ubiquitinated and targeted by the selective autophagy receptor p62 and autophagic degradation, leading to decreased survival as compared with wild-type (WT) bacteria. (pubmedcentralcanada.ca)
  • A new era of autophagy research began in 1990s when several groups of scientists independently discovered autophagy-related genes using the budding yeast . (wikipedia.org)
  • A unified nomenclature was advocated in 2003 by the yeast researchers to use ATG to denote autophagy genes. (wikipedia.org)
  • Knowledge of ATG genes provided scientists more convenient tools to dissect functions of autophagy in human health and disease. (wikipedia.org)
  • Since the discovery of autophagy-related ( Atg ) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. (nature.com)
  • Table 1 summarizes the association between genetic variants of autophagy-related genes and selected human diseases. (nature.com)
  • The broad objectives of the Xavier lab are to identify new candidate host genes and pathways that contribute to the induction of autophagy (perform genome-wide CRISPR screens, biochemical analysis, and analysis of mutant animals to define target mechanisms), and to develop successful strategies to increase autophagy in cells, thereby leading to new strategies to treat infectious diseases and disorders of mucosal immunity. (genomeweb.com)
  • We detail the ever increasing list of neurodegenerative diseases in which autophagy perturbations have been reported and discuss a new class of diseases caused by mutations in core autophagy genes. (jci.org)
  • Autophagy is carried out by a set of more than 30 proteins encoded by the Autophagy‐Related genes ( ATGs ), the functions of which have been dissected using genetic and biochemical approaches. (els.net)
  • lncreasingly, it is becoming clear that proteins encoded by ATG genes carry out functions in cellular pathways independent of their roles in autophagy. (els.net)
  • The identification of autophagy-related genes in yeast in the 1990s allowed researchers to deduce the mechanisms of autophagy, which eventually led to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi. (wikipedia.org)
  • Light-dependent retinal degeneration in the Drosophila visual system is caused by the knockdown or mutation of autophagy-essential components, such as autophagy-related protein 7 and 8 (atg-7/atg-8), or genes essential for PE (phosphatidylethanolamine) biogenesis and autophagosome formation, including Phosphatidylserine decarboxylase (Psd) and CDP-ethanolamine:diacylglycerol ethanolamine-phosphotransferase (Ept). (mendeley.com)
  • It is tightly regulated by almost 40 different ATG (Autophagy) genes. (thefreelibrary.com)
  • The transcription factor EB (TFEB), a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes. (sciencemag.org)
  • More than 31 autophagy-related genes (ATG) whose products regulate autophagy have been identified, primarily through yeast genetics, and several have mammalian counterparts ( 3 ). (pnas.org)
  • Recent studies have not only identified a large number of autophagy genes (ATGs) but also expanded the autophagic cargos from intracellular pathogens to misfolded proteins ( 15 - 18 ). (pnas.org)
  • Like all important cellular processes, autophagy is complex, regulated by a web of genes and proteins. (fightaging.org)
  • Following early studies that displayed similarities between yeast and mammalian macroautophagy (hereafter autophagy) ( 9 ), extensive studies in yeast revealed more than 30 atg genes that orchestrate autophagy. (diabetesjournals.org)
  • The molecular basis of autophagosome formation was largely demonstrated in budding yeast through the identification of autophagy-related ATG genes (ScATGs). (frontiersin.org)
  • The orthologues of ScATGs that function for autophagosome formation are conserved in plant species, and therefore the studies using the mutants of these ATG genes in model plants has helped develop our understanding of plant autophagy. (frontiersin.org)
  • The molecular machinery of autophagy was largely discovered in yeast and is directed by a number of autophagy-related (Atg) genes. (cellsignal.com)
  • Several genes involved in tumor suppression and/or are associated with cancer susceptibility are also regulators of autophagy. (biolegend.com)
  • He discovered specific genes involved in the regulation of autophagy. (care2.com)
  • Several Parkinson's risk genes, including LRRK2, have been previously linked to autophagy, a waste disposal system inside cells (see ARF related news story ). (alzforum.org)
  • The molecular processes and signalling pathways controlling autophagy include numerous autophagy-related (Atg) genes, important stress-inducible intracellular protein, such as p62/A170/SQSTM1 and autophagosome localizing proteins such as LC3, among many others making this a complex network of control. (horizondiscovery.com)
  • Furthermore, SNPs and mutations in genes encoding proteins involved in autophagy have been implicated in a wide variety of conditions including asthma, Crohn's disease and cancers. (horizondiscovery.com)
  • The gene regulations were then related to the biological processes by the study of signaling pathways that showed the induction of autophagy-related genes in early transfection. (sigmaaldrich.com)
  • The role of autophagy-related genes (Atgs) in basal, starvation, and stress-induced autophagy in mammalian cells. (uio.no)
  • After the Nobel Prize was awarded for the discovery of autophagy genes in 2016, several biotech companies launched with plans to develop drugs that either boost or inhibit autophagy to treat a bevy of diseases, including Alzheimer's and cancer. (acs.org)
  • The contributors describe strategies for identifying and evaluating the biochemical and morphological changes that occur during apoptosis, autophagy, necrosis, and other forms of cell death, as well as for pinpointing the genes and proteins that may be involved. (cshlpress.com)
  • and (3) identify small molecules that target selective autophagy. (genomeweb.com)
  • Presents detailed information on the role of mitophagy, the selective autophagy of mitochondria, in health and disease, by delivering an in-depth treatment of the molecular mechanisms involved in mitophagy initiation and execution, as well as the role of mitophagy in Parkinson Disease, cardiac aging, and skeletal muscle atrophy. (elsevier.com)
  • Recent studies have identified several types of selective autophagy processes in plant cells that degrade specific organelles or unwanted components. (frontiersin.org)
  • We hope that this Research Topic will successfully show the recent advances of the studies on the role of plant selective autophagy throughout plant development, and help a large number of researchers to explore new avenues towards the further development of related fields. (frontiersin.org)
  • Given the role of autophagy and selective autophagy in several disease related processes such as tumorigenesis, neurodegeneration and infections, it is very important to dissect the molecular mechanisms of selective autophagy, in the context of the system and the organism. (mdpi.com)
  • However, the mechanisms of selective autophagy in Drosophila have been largely unexplored. (mdpi.com)
  • Luhr M, Szalai P, Sætre F, Gerner L, Seglen PO, Engedal N. A simple cargo sequestration assay for quantitative measurement of non-selective autophagy in cultured cells. (uio.no)
  • [16] [17] This was the first time the fact that lysosomes were established as the sites of intracellular autophagy. (wikipedia.org)
  • Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). (nature.com)
  • There are usually intracellular stimuli and signals that induce autophagy. (news-medical.net)
  • Crotzer VL, Blum JS (2005) Autophagy and intracellular surveillance: modulating MHC class II antigen presentation with stress. (springer.com)
  • An immunological role of autophagy was first recognized with the discovery of autophagy's ability to sanitize the cellular interior by killing intracellular microbes. (springer.com)
  • This was the first time the fact that lysosomes are the sites of intracellular autophagy was established. (wikipedia.org)
  • Paradoxically, autophagy is a "double-edged sword" because it eliminates some pathogens, whereas it can be used by some intracellular pathogens to multiply and cause infection. (elsevier.com)
  • In Sindbis virus, tobacco mosaic virus, herpes simplex virus type 1 (HSV-1) and several bacterial infections, autophagy may have a protective function by restricting intracellular pathogen replication or by ensuring the survival of infected and/or uninfected cells ( 4 ). (pnas.org)
  • Traditionally, autophagy was considered a one-lane system for protein turnover and a mechanism for replenishing the intracellular amino acid pool during starvation. (diabetesjournals.org)
  • Autophagy is a process that degrades and removes dysfunctional proteins, damaged organelles, and intracellular pathogens by delivering cytoplasmic material to the lysosome. (biolegend.com)
  • Intracellular components are delivered by chaperone-mediated autophagy (CMA) 1 ( 4 ), microautophagy ( 5 ), or macroautophagy ( 6 , 7 ), hereafter referred to as autophagy. (mcponline.org)
  • A ligand library interfering with the detected intracellular pathways showed concentration-dependent effects on the transfection efficiency of splice correction oligonucleotide complexed with PepFect14, proving that the autophagy process is induced upon the uptake of complexes. (sigmaaldrich.com)
  • There are both constitutive and stress-induced pathways for autophagy in neurons, which catalyze the turnover of aged or damaged mitochondria, endoplasmic reticulum, other cellular organelles, and aggregated proteins. (nih.gov)
  • The protein kinase complex, mTORC1, made up of the catalytic subunit, Target of Rapamycin (TOR), the Raptor regulatory/scaffold subunit and other proteins plays the central role in the signaling pathways involved in regulation of autophagy. (els.net)
  • Accumulation of activated rhodopsin in some Drosophila mutants leads to retinal degeneration, and although it is known that activated rhodopsin is degraded in endosomal pathways in normal photoreceptor cells, the contribution of autophagy to rhodopsin regulation has remained elusive. (mendeley.com)
  • This study reveals that activated rhodopsin is degraded by autophagy in collaboration with endosomal pathways to prevent retinal degeneration. (mendeley.com)
  • Here, we provide an integrated review of recent studies implicating autophagy dysfunction in the progression of mammalian disorders and summarize research suggesting that the molecular pathways involved in autophagy could serve as potential therapeutic targets. (royalsocietypublishing.org)
  • First, signal transduction pathways, frequently regulated by mTOR, initiate autophagy in response to a stimulus. (royalsocietypublishing.org)
  • Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. (mdpi.com)
  • Finally, emerging evidence suggests that cross-talk exists between apoptotic and autophagic pathways, in that established regulators of apoptosis, such as the tumor suppressor p53 and antiapoptotic Bcl-2 family members, also regulate autophagy. (mdanderson.org)
  • Autophagy products feed into cellular energy-generation pathways, facilitating cell survival under stressful conditions. (thefreelibrary.com)
  • Moreover, autophagy has been described as one of the central pathways for liver health and disease. (thefreelibrary.com)
  • Therefore, a comprehensive understanding of autophagy pathways that are operational in HCCs may be most rewarding, allowing development of new diagnosis and treatment techniques. (thefreelibrary.com)
  • These protein complexes play key roles in the regulation of cellular growth, cell-cycle progression, cell migration, and protein synthesis as well as the coordination of the catabolic autophagy activation with the activity of these essential cellular anabolic pathways. (thefreelibrary.com)
  • These pathways also represent important regulators of cell growth and proliferation, motility, mitochondrial function, autophagy, and survival ( 1 - 4 ). (diabetesjournals.org)
  • Interestingly, autophagy is regulated by the above-mentioned nutrient-sensing pathways ( 9 - 11 ). (diabetesjournals.org)
  • Here, we provide a review and perspective regarding the potential actions of nutrient-sensing pathways and autophagy in diabetic nephropathy. (diabetesjournals.org)
  • In cell biology research it seems that building gets more attention than destruction: work on the cell cycle leapt ahead while apoptosis research was in its infancy, and protein synthesis pathways were well established when autophagy was, for most researchers, a word that drew blank stares. (rupress.org)
  • In conditions of starvation, autophagy is boosted to produce amino acids and ATP for cell survival, but in the presence of growth factors, autophagy pathways are shut off. (biolegend.com)
  • Three main autophagy pathways have been described: macroautophagy, microautophagy, and chaperone-mediated autophagy. (biolegend.com)
  • Animal and human studies have shown that autophagy is protective against neurodegeneration, and defects in autophagy pathways are associated with diseased brains. (biolegend.com)
  • Therapies that activate the autophagy pathways are therefore being investigated as treatments for neurodegenerative diseases. (biolegend.com)
  • That autophagy represents a point of convergence for the secretory and the endosomal pathways suggests a number of interesting implications for immunity. (jimmunol.org)
  • However, one common element of autophagy pathways involves the importation of cytoplasmic components into the lysosome. (sigmaaldrich.com)
  • macroautophagy , microautophagy , and chaperone-mediated autophagy (CMA). (wikipedia.org)
  • Cuervo AM, Wong E. Chaperone-mediated autophagy: roles in disease and aging. (springer.com)
  • The term autophagy describes a range of processes, including chaperone-mediated autophagy, microautophagy, and macroautophagy. (jci.org)
  • Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy. (wikipedia.org)
  • There are three types of autophagy: ​Macroautophagy, microautophagy, and chaperone-mediated autophagy. (abcam.com)
  • There are several different types of autophagy: macroautophagy, chaperone-mediated autophagy (CMA), microautophagy and non-canonical autophagy, such as LC3-associated phagocytosis (LAP) [ 3 ]. (royalsocietypublishing.org)
  • Mammalian cells exhibit three distinct forms of autophagy to deliver cytosolic cargo to the lysosomes, namely, macroautophagy, chaperone-mediated autophagy, and microautophagy ( 1 ). (diabetesjournals.org)
  • The second form of autophagy, chaperone-mediated autophagy, displays functional selectivity for the lysosomal targeting of specific soluble cytosolic proteins with the KFERQ signature ( 7 ) and requires the lysosome-associated membrane protein-2A receptor ( 7 ). (diabetesjournals.org)
  • Chaperone-mediated autophagy utilizes heat shock proteins and transporters on lysosomal membranes to degrade proteins that express a targeting motif, making it a highly specific process. (biolegend.com)
  • Chaperone-mediated autophagy is regulated by environmental stress, and LAMP-2A expression levels can dictate the rate at which it occurs. (biolegend.com)
  • They are chaperone-mediated autophagy, microautophagy, and macroautophagy. (sigmaaldrich.com)
  • Chaperone-mediated autophagy (CMA) involves the direct translocation of cytosolic proteins across the lysosomal membrane. (sigmaaldrich.com)
  • Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. (nature.com)
  • Regulation of autophagy is genetically linked. (news-medical.net)
  • Here we review the mechanisms and regulation of autophagy in embryonic stem cells, hematopoietic stem cells, mesenchymal stem cells, neural stem cells, and cancer stem cells. (springer.com)
  • An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. (springer.com)
  • With the explosion of information on autophagy in cancer, this is an opportune time to speed the efforts to translate our current knowledge about autophagy regulation into better understanding of its role in cancer. (springer.com)
  • This book will cover the latest advances in this area from the basics, such as the molecular machinery for autophagy induction and regulation, up to the current areas of interest such as modulation of autophagy and drug discovery for cancer prevention and treatment. (springer.com)
  • There will be ten sessions on topics such as Activation and deactivation of GTPases, Regulation of and by post translational modifications, Structural and molecular mechanisms, Small GTPases in the endocytic system, Small GTPases in the secretory system, Small GTPases in membrane trafficking in specialized cells, Autophagy, Rag GTPases, and GTPases and disease. (eurekalert.org)
  • This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. (mdpi.com)
  • Such specific regulation of autophagy may also be important for cell types in the muscle, brain and pancreas," said Dr. Min Chen, assistant professor of immunology at BCM and a corresponding author of this work. (medgadget.com)
  • This article comments on the fundamental developments on roles for autophagy in metabolic regulation and discusses currently available methods to monitor autophagy. (diabetesjournals.org)
  • The kinase mTOR is a critical regulator of autophagy induction, with activated mTOR (Akt and MAPK signaling) suppressing autophagy, and negative regulation of mTOR (AMPK and p53 signaling) promoting it. (cellsignal.com)
  • The regulation of autophagy has attracted more and more attention with the promise for improving treatment of diseases as a potential therapeutic target. (rsc.org)
  • In this study, the effects of Fe-MIL-101_NH 2 on mouse embryonic fibroblasts (MEFs) were investigated and the potential applications of these nanoparticles in the regulation of autophagy were explored. (rsc.org)
  • Regulation of autophagy by calcium perturbation and signaling from ER stress / the unfolded protein response (UPR) in malignant and nonmalignant cells. (uio.no)
  • Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. (nature.com)
  • Inhibition of autophagy leads to increased TG accumulation. (nature.com)
  • Inhibition of autophagy decreases TG β-oxidation and decay. (nature.com)
  • Genetic inhibition of autophagy induces degenerative changes in mammalian tissues that resemble those associated with aging, and normal and pathological aging are often associated with a reduced autophagic potential. (nih.gov)
  • Pharmacological or genetic manipulations that increase life span in model organisms often stimulate autophagy, and its inhibition compromises the longevity-promoting effects of caloric restriction, Sirtuin 1 activation, inhibition of insulin/insulin growth factor signaling, or the administration of rapamycin, resveratrol, or spermidine. (nih.gov)
  • Inhibition of AMPK-mediated autophagy led to reduced lung branching in vitro. (jci.org)
  • Many, if not most chemotherapeutic drugs and radiation also promote autophagy, which is generally considered a cytoprotective response, in that its inhibition frequently promotes apoptotic cells death. (mdpi.com)
  • Crocin has a paradoxical protective effect by regulating both the induction and inhibition of autophagy in ischemia and reperfusion injury. (greenmedinfo.com)
  • Here, we discuss the molecular mechanism of ER stress and autophagy and their induction and inhibition signaling network. (intechopen.com)
  • Autophagy inhibition enhanced 5FUinduced cell death in human gast. (ingentaconnect.com)
  • Additionally, inhibition of autophagy by either 3MA or beclin1 ablation increased 5FUinduced cell death in BGC823 cells. (ingentaconnect.com)
  • Autophagy inhibition through manipulation of sirtuin proteins may increase the therapeutic efficacy of the 5FU chemotherapeutic drug against gastric carcinoma. (ingentaconnect.com)
  • Furthermore, pharmacological inhibition of mammalian target of rapamycin with Torin1 also was not sufficient to markedly upregulate neuronal autophagy. (jneurosci.org)
  • Neuronal autophagy is not robustly upregulated in response to starvation or mammalian target of rapamycin inhibition, suggesting that constitutive autophagy in neurons maintains homeostasis by playing an integral role in regulating the quality of the neuronal proteome. (jneurosci.org)
  • A Novel Role of Listeria monocytogenes Membrane Vesicles in Inhibition of Autophagy and Cell Death. (uio.no)
  • Moreover, inhibition of both ER stress and autophagy promote the sensitivity of melanoma cells to dabrafenib. (dovepress.com)
  • These results provide us with promising evidence that the inhibition of autophagy and ER stress could serve a therapeutic effect for the conventional dabrafenib chemotherapy. (dovepress.com)
  • The inhibition of autophagy through chloroquine had no effect on the genotoxicity induced by the tested compounds, but it led to a high increase of cytotoxicity. (musicaenlamochila.net)
  • Historically known for its anti-malarial activity, chloroquine is a widely used biological research tool for studying autophagy inhibition. (musicaenlamochila.net)
  • Chloroquine diphosphate is an inhibitor of autophagy and toll-like receptors (TLRs) Accordingly, we found that the autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specific autophagy regulators synergistically enhanced the ability of ERK inhibitors to. (musicaenlamochila.net)
  • ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. (springer.com)
  • Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. (mdpi.com)
  • However, in spite of the constitutive activation of mTOR and the abrogated autophagy activity in TSC1- or TSC2-deficient cells, the TSC mutant cells are defective in aggresome formation and undergo apoptosis upon misfolded protein accumulation both in vitro and in vivo. (pnas.org)
  • The mammalian target of rapamycin (mTOR) integrates diverse signals to regulate fundamental cellular processes, such as translation, cell growth, autophagy, and stress response ( 5 , 6 ). (pnas.org)
  • However, opposite to AMPK, mTOR actually inhibits autophagy. (care2.com)
  • In general, once you ve depleted the glycogen stores in your liver, AMPK is activated, mTOR is suppressed and autophagy kicks in ( 7 ). (care2.com)
  • mTOR is a key regulator of autophagy. (sigmaaldrich.com)
  • Under normal physiological conditions mTOR inhibits autophagy, but, under extreme nutritional deficiency mTOR can be inactivated, which leads to autophagy activation. (sigmaaldrich.com)
  • mTOR activity negatively regulates autophagy, which may involve AMP kinase induced phosphorylation of mTOR on specific sites. (sigmaaldrich.com)
  • Autophagy can also be induced in mTOR-independent manner by lowering the levels of myo-inositol-1, 4, 5-triphosphate in cells by using lithium, carbamezapine, or sodium valproate. (sigmaaldrich.com)
  • The importance of autophagy for maintaining quality control on proteins and organelles is underscored by the fact that many diseases exhibit dysfunctional autophagic activities, for example neurodegenerative diseases. (els.net)
  • Describes the various aspects of the complex process of autophagy in a myriad of devastating human diseases, expanding from a discussion of essential autophagic functions into the role of autophagy in proteins, pathogens, immunity, and general diseases. (elsevier.com)
  • This review will describe autophagic cell death induced in breast tumor cells, lung cancer cells as well as glioblastoma, demonstrating that it cannot be concluded that stress induced autophagy is, of necessity, cytoprotective in function. (mdpi.com)
  • In contrast, overactivation of autophagy may indeed lead to cell death through so far not well understood mechanisms as an alternative nonapoptotic programmed cell death mechanism, "autophagic cell death" has been reported to be responsible for killing cells in a number of scenarios (2-4). (thefreelibrary.com)
  • In this review, we will briefly introduce the basic autophagic machinery and autophagy-cell death connections and summarize implication of autophagy-related cell death and survival for HCC management. (thefreelibrary.com)
  • The endoplasmic reticulum was proposed as the source of the autophagic membranes (Dunn, 1990), although uncertainties about this and other details of autophagy remain. (rupress.org)
  • Decreased autophagic function can result from gene mutations that inhibit autophagosome maturation and lysosome fusion, or from aging-related declines in CNS expression of autophagy proteins. (biolegend.com)
  • In this Brief Review , we cover the immunological roles of macroautophagy ( 1 ), a specific autophagic process that will be referred to herein as sensu stricto autophagy or simply autophagy. (jimmunol.org)
  • An excellent genetically tractable model organism to study autophagy is Drosophila , which appears to have a highly conserved autophagic machinery compared with mammals. (mdpi.com)
  • Autophagy is induced upon cellular stress, such as starvation, organelle damage, pathogen invasion, and oxidative stress ( 11 ), and serves as a prosurvival response because mice with a defect in the autophagic response die upon neonatal starvation ( 12 ). (mcponline.org)
  • An advantage to monitoring p62 to measure autophagic flux is that lysosomal inhibitors are not necessary, because unlike LC3-II, p62 does not usually increase when autophagy is induced. (musicaenlamochila.net)
  • Cited by: 248 Publish Year: 2008 Author: Eri Iwai-Kanai, Hua Yuan, Chengqun Huang, M. and the lysosomotropic drug chloroquine could be used to measure autophagic flux in both in vitro and in vivo model systems Chloroquine (CQ) is an antimalarial drug and late-stage inhibitor of autophagy currently FDA-approved for use in the treatment of autophagy flux chloroquine rheumatoid arthritis and other autoimmune diseases. (musicaenlamochila.net)
  • The Autophagy Team aims to understand central regulatory mechanisms and mediators of autophagic processes in mammalian cells. (uio.no)
  • This review focuses on the role of macroautophagy (hereafter referred to as autophagy) in human diseases. (nature.com)
  • Here we focus on macroautophagy, which we refer to as autophagy. (jci.org)
  • Although most types of autophagy occur in most eukaryotic cells, the term 'autophagy' is commonly used to describe macroautophagy (and will be used herein). (royalsocietypublishing.org)
  • However, it is now becoming increasingly clear that autophagy, in particular macroautophagy, exhibits significant versatility in its ability to degrade mitochondria (mitophagy), endoplasmic reticulum (reticulophagy), ribosomes (ribophagy), and peroxisomes (pexophagy) ( 1 ). (diabetesjournals.org)
  • Proper activation of autophagy can maintain neuronal health through several mechanisms, including aggrephagy and mitophagy , both of which are forms of selective macroautophagy. (biolegend.com)
  • Macroautophagy (hereafter autophagy) is a conserved homeostatic process that occurs in all eukaryotes. (pubmedcentralcanada.ca)
  • Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. (hindawi.com)
  • Numerous stimuli can induce autophagy - for example hypoxia and nutrient starvation - which enable the cell to free vital amino acids to re-use as well as clear aberrant structures or organelles. (abcam.com)
  • Many stressors, such as starvation, ischaemia and oxidative stress can induce autophagy. (royalsocietypublishing.org)
  • Under certain conditions, autophagy can also induce programmed cell death ( apoptosis ). (rxlist.com)
  • Intermittent fasting is a possible way to induce autophagy. (rxlist.com)
  • A currently popular diet known as the ketogenic diet , in which 75% of the daily calories come from fat, is believed to induce ketosis and autophagy. (rxlist.com)
  • For instance, fasting may induce autophagy in any type of cell and not necessarily in fat cells. (rxlist.com)
  • However, do not attempt to fast to induce autophagy without discussing this method with your doctor . (rxlist.com)
  • Furthermore, it has been shown that conventional chemotherapeutic drugs and radiation alone rarely induce a form of autophagy that leads to cell death. (mdpi.com)
  • The UPR and autophagy are interlinked, which indicates that the ER stress can not only induce autophagy but also suppress it. (intechopen.com)
  • Surprisingly, starvation did not induce autophagy in either the axonal or somatodendritic compartment. (jneurosci.org)
  • Histone deacetylase (HDAC) inhibitors (HDI) induce endoplasmic reticulum (ER) stress and apoptosis, while promoting autophagy, chloroquine and autophagy inhibitor which promotes cancer cell survival when apoptosis is compromised. (musicaenlamochila.net)
  • Host defence mechanism - autophagy helps kill cells that are infected or invaded by foreign pathogens. (news-medical.net)
  • Although the changes are quite subtle, there are differences between the way that fibroblasts that contain mutant LRRK2 respond to being starved - suggesting that there may be changes in the way that these cells regulate a key process called autophagy (a term which comes from the greek meaning to eat yourself, and is one of the ways that cells get rid of waste and recycle proteins and organellles). (ucl.ac.uk)
  • Autophagy is particularly important in neurons, which are terminally differentiated cells that must last the lifetime of the organism. (nih.gov)
  • It helps us understand the relationship between autophagy and stem cells. (springer.com)
  • Autophagy is a specific universal biological phenomenon in eukaryotic cells, which is characterized by cytoplasmic vacuoles in the process of degrading cellular contents in lysosomes. (springer.com)
  • This process of autophagy ( 2 ), however, poses a problem for the body's specialized fuel-sensing cells. (sciencemag.org)
  • 4 ) show how β cells avoid inappropriate autophagy, and describe a form of this process tailored to the needs of these cells. (sciencemag.org)
  • Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. (hindawi.com)
  • Autophagy, a catabolic process by which cells develop, differentiate, survive, and stay homeostasis under conditions such as nutrients deprivation and hypoxia, has been implicated in many liver diseases including viral hepatitis, alcohol liver diseases, nonalcohol liver diseases, acute liver injury, and alpha1-antitrypsin (AT) deficiency related liver diseases [ 2 - 5 ]. (hindawi.com)
  • Autophagy, a metabolic process that eukaryotic cells digest their own organelles and long-lived proteins, is critical for development, differentiation, and homeostasis. (hindawi.com)
  • These pages will serve as a description on how the pro-survival function of autophagy may help cancer cells resist chemotherapy and radiation treatment as well as how the pro-death functions of autophagy may enhance cell death in response to cancer therapy, and how to target autophagy for cancer prevention and therapy − what to target and how to target it. (springer.com)
  • Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. (springer.com)
  • Our studies revealed an unexpected finding where one cell triggers autophagy in neighboring cells. (umassmed.edu)
  • Autophagy is the process cells use to degrade used or damaged components inside the cell for recycling. (umassmed.edu)
  • A breakdown in autophagy is associated with diseases such as cancer, immune disorders and neurodegeneration, but little is known about the system-wide signals between cells that control autophagy in complex, multicellular animals. (umassmed.edu)
  • When Baehrecke and colleagues turned off the Mcr gene in Drosophila salivary gland cells, fragments consistent with a breakdown in autophagy appeared, indicating that Mcr played a role in the clearance of cellular debris by activating autophagy. (umassmed.edu)
  • 2021. "Advances in Plant Autophagy" Cells 10, no. 1: 194. (mdpi.com)
  • Autophagy is the process of 'self-eating' that cells go through, destroying their own contents and recycling certain components. (siliconrepublic.com)
  • Referring to his work as part of a "series of brilliant experiments", the Nobel Foundation said Ohsumi subsequently showed that sophisticated machinery is used in humans cells to achieve autophagy. (siliconrepublic.com)
  • Autophagy can provide fuel for renewal of cells, alleviating against starvation and fighting against viruses and bacteria. (siliconrepublic.com)
  • In autophagy, cells engulf unwanted material in vesicles that are then deposited in a trash bin called the vacuole or lysosome. (genengnews.com)
  • Autophagy serves on the one hand for the recycling of the building blocks of cells and the provision of energy, but is also activated specifically in stress situations. (medindia.net)
  • Autophagy is a natural cellular mechanism by which the cells in our body degrade unnecessary or damaged components within the cell. (rxlist.com)
  • Though autophagy sounds like self-destruction, the process actually helps clean up harmful material inside the cells and rejuvenates them. (rxlist.com)
  • In times of stress , when cells are deprived of nutrients or oxygen , autophagy can provide an alternate source of energy from the recycled cellular material to help them survive. (rxlist.com)
  • Autophagy forms a part of the metabolic process which helps cells convert food into a form of energy that cells can use to grow and divide. (rxlist.com)
  • When fasting starves the cells, autophagy helps digest some of the cell components, to provide the necessary energy for survival. (rxlist.com)
  • It is also not clear what type of cells initiate autophagy in response to fasting. (rxlist.com)
  • Autophagy therefore plays an important role during tumorigenesis, as it allows early solid tumors to survive prior to vascularization (angiogenesis), and it promotes chemoresistance by allowing tumor cells to remove damaged proteins and organelles. (mdanderson.org)
  • A process of self-digestion called autophagy prompts the maturation of red blood cells. (medgadget.com)
  • When other cells get old or stressed, their organelles may become damaged and need to be cleared by autophagy for quality control. (medgadget.com)
  • Autophagy is a catabolic response of cells to stress. (thefreelibrary.com)
  • Autophagy is active at a basal level in cells, and it may further be upregulated in response to several types of stresses that disturb cellular homeostasis, including low cellular ATP levels, nutrient and growth factor deprivation, hypoxic conditions, endoplasmic reticulum (ER) stress, pathogen entry, or anticancer drug treatment (1). (thefreelibrary.com)
  • A number of studies showed that during transitions from normal cells to cancer cells, autophagy either plays a tumor-suppressor role or prevents cancer formation. (thefreelibrary.com)
  • Sirt1 induction of autophagy occurred at the level of autophagosome maturation and completion in cultured prostate cancer cells. (wellnessresources.com)
  • Capsaicin inhibits 5-FU-induced autophagy and rendering Cholangiocarcinoma cells more susceptible to 5-FU-induced apoptosis. (greenmedinfo.com)
  • An antioxidant-rich extract of seaweed polyphenols combined with current PC treatment modalities may inhibit tumor relapse by targeting therapy-orchestrated autophagy in residual cells. (greenmedinfo.com)
  • TSC Null Cells Are Aggresome-Defective Despite Abrogated Autophagy. (pnas.org)
  • If you don't know, autophagy is the process by which your body cleans out old, damaged structures and cells to make room for the new, healthy ones. (robbwolf.com)
  • Autophagy is, broadly speaking, the process by which your cells recycle damaged components. (fightaging.org)
  • Scientists believe that a number of the benefits of calorie restriction result from an increased level of autophagy , producing a lower level of damage in your cells at any given point in time. (fightaging.org)
  • Autophagy is an essential cellular process by which cells take out the trash, so to speak. (abovetopsecret.com)
  • The effects of prolonged fasting on the immune system, namely, how it clears away damaged white blood cells via autophagy and how this causes hematopoietic stem cells to self renew and make more stem cells and also produce new blood cells to fully replenish the white blood cell population. (abovetopsecret.com)
  • Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. (frontiersin.org)
  • Autophagy is the "self-eating process" that degrades the portion of cytoplasm including organelles in eukaryotic cells. (frontiersin.org)
  • Dysregulation of autophagy can have fatal consequences for cells, which is why it has been linked to diseases like cancer, neurodegeneration, and pathogenic infections. (biolegend.com)
  • These protein aggregates become too large to pass through the pore of the proteasome, so cells rely on autophagy for their removal to maintain health. (biolegend.com)
  • Greek for self-eating, autophagy is a natural cleansing process in the body that allows cells to essentially eat themselves. (care2.com)
  • In fact, autophagy is essential to our survival cells would not thrive or survive without it. (care2.com)
  • One study to support this found that the cells of long-living individuals (people age 100 and over) showed higher rates of autophagy than younger seniors (at 75 years old) ( 1 ). (care2.com)
  • It is of note that the 5FU treatment only promoted autophagy in BGC823 cells. (ingentaconnect.com)
  • As a result, autophagy is now recognized to be another barrier confronted by microbes that invade eukaryotic cells. (jimmunol.org)
  • The autophagy narrative has become a hot topic in PD research, since a blockage in this process may help explain why cells accumulate α-synuclein deposits. (alzforum.org)
  • In mammalian cells, Wolozin showed that one such gene, histone deacetylase 6 (HDAC6), directly binds LRRK2 and mediates the ability of the G2019S LRRK2 mutant to dial down autophagy. (alzforum.org)
  • Paradoxically, autophagy is not only a major mechanism by which a starving cell reallocates nutrients to ensure survival, scientists are now demonstrating that autophagy also provides cells that cannot undergo apoptosis with an alternate form of self-destruction. (science20.com)
  • For instance, in vitro and animal and human studies indicate that autophagy dysfunction in bone cells is associated with the onset of bone diseases such as osteoporosis. (scielo.br)
  • Moreover, we found a greater accumulation of LC3-II after exposure to an autophagy inhibitor, chloroquine (CQ), combined with Gd 3+ than that after exposure to CQ alone, suggesting that Gd 3+ activated autophagy in HEK293 cells. (musicaenlamochila.net)
  • Therefore, it is interesting and significant to study the effects of MOFs on living cells from safety aspects as well as the therapeutic viewpoint, especially their effects on autophagy which have not been reported yet. (rsc.org)
  • In autophagy cells destroy their own cytoplasmic components in a very systematic manner and recycle them. (sigmaaldrich.com)
  • In mammalian cells, autophagy occurs constitutively at basal rates and its primary function is to protect cells under stress conditions. (sigmaaldrich.com)
  • However, if cellular damage becomes irreparable, cells can destroy themselves completely by autophagy. (sigmaaldrich.com)
  • Autophagy occurs in organisms as simple as yeast cells and as complex as human beings. (innovations-report.com)
  • Even entire cellular organelles can be removed by autophagy when they do not function properly any longer and viruses or bacteria that invade cells can be neutralized. (innovations-report.com)
  • The components recovered in the process can then be reused by cells as basic material, which is why autophagy is also employed as a strategy for cell survival when the energy supply is low. (innovations-report.com)
  • As it has become increasingly clear that the cells can target the process and that its disturbance is associated with an entire series of disorders, autophagy research has really taken off," explained Professor Christian Behl, Deputy Speaker of the CRC and Director of the Institute of Pathobiochemistry at the Mainz University Medical Center. (innovations-report.com)
  • On the other hand, cancer cells make use of autophagy processes in order to survive the nutrient shortage associated with fast tumor growth. (innovations-report.com)
  • Torgersen ML, Engedal N, Boe SO, Hokland P, Simonsen A. Targeting autophagy potentiates the apoptotic effect of histone deacetylase inhibitors in t(8;21) AML cells. (uio.no)
  • Our studies support that both endoplasmic reticulum (ER) stress and autophagy were induced in the melanoma cells after the treatment with dabrafenib. (dovepress.com)
  • In addition, ER stress-induced autophagy protects melanoma cells from the toxicity of dabrafenib. (dovepress.com)
  • Taken together, the data suggest that ER stress-induced autophagy determines the sensitivity of melanoma cells to dabrafenib. (dovepress.com)
  • It is critical to the healthy functioning of cells and the failure of autophagy is a major reason for the accumulation of cell damage and aging. (thermofisher.com)
  • Finally, we discuss the role of autophagy in neuronal development, homeostasis, and aging and the links between deficits in autophagy and neurodegeneration. (nih.gov)
  • Therefore, exploring the mechanism of autophagy in maintaining stem cell homeostasis is crucial. (springer.com)
  • Although the importance of autophagy for cell homeostasis and survival has long been appreciated, our understanding of how autophagy is carried out at the molecular level has recently benefited from genetic studies that have revealed the functions of many of the participating proteins. (els.net)
  • therefore, autophagy acts as a housekeeping mechanism to maintain cellular homeostasis. (royalsocietypublishing.org)
  • The process of autophagy helps maintain normal functioning ( homeostasis ) in the cell. (rxlist.com)
  • In short, autophagy is a part of a cellular process that maintains cell homeostasis by finding a balance between making and breaking cellular components. (rxlist.com)
  • Autophagy is a Greek-derived concept that means "self-eating" and is increasingly recognized as an important regulator of homeostasis and disease. (jci.org)
  • In addition to its cellular homeostasis function, autophagy is emerging as a central component of antimicrobial host defense against diverse infections. (pnas.org)
  • Other intersections of autophagy with immune processes encompass effects on inflammasome activation and secretion of its substrates, including IL-1β, effector and regulatory interactions with TLRs and Nod-like receptors, Ag presentation, naive T cell repertoire selection, and mature T cell development and homeostasis. (jimmunol.org)
  • Moreover, recent studies have shown that autophagy plays an important role for the maintenance of bone homeostasis. (scielo.br)
  • Autophagy plays a central role in normal development and cell homeostasis of yeast. (genome.jp)
  • In addition, exercise is not able to lower serum lipids as effectively in the mutant mice, highlighting the importance of autophagy for the beneficial effects of exercise on glucose and lipid homeostasis. (pubmedcentralcanada.ca)
  • Interestingly, mutant mice fed a high-fat diet but not exercised are largely indistinguishable from wild-type mice regarding these metabolic parameters, suggesting that basal autophagy does not contribute substantially to resting lipid or glucose homeostasis. (pubmedcentralcanada.ca)
  • To investigate how a defect in autophagy translates into this type of metabolic disorder, the authors focus on AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis. (pubmedcentralcanada.ca)
  • These Atg proteins form distinct functional complexes that regulate each step of the process, including induction of autophagy, generation of the nucleation complex, autophagosome formation, and cargo recognition ( 1 ). (diabetesjournals.org)
  • This information is important because one of the major functions of autophagy is to degrade and eliminate excessive, old, and harmful materials from the cell. (elsevier.com)
  • In disease, autophagy has been seen as an adaptive response to stress, which promotes survival, whereas in other cases it appears to promote cell death and morbidity . (wikipedia.org)
  • Autophagy plays an important role in the survival of cellular organisms. (news-medical.net)
  • Mazure NM, Pouysségur J (2010) Hypoxia-induced autophagy: cell death or cell survival? (springer.com)
  • As a necessary process to maintain cell survival during starvation and damage, the proteins involved in autophagy are highly conserved from yeast to mammalian. (hindawi.com)
  • The text will include an explanation on how autophagy can function in both oncogenesis and tumor suppression and a description of its function in tumor development and tumor suppression through its roles in cell survival, cell death, cell growth as well as its influences on inflammation, immunity, DNA damage, oxidative stress, tumor microenvironment, etc. (springer.com)
  • Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. (mdpi.com)
  • Autophagy is a process of cellular self-digestion, whereby the cell degrades subcellular materials in order to generate energy and metabolic precursors in order to prolong survival, classically under conditions of nutrient deprivation. (mdpi.com)
  • Autophagy, on the other hand, is primarily a cell survival rather than a cell death process. (mdanderson.org)
  • It is important to understand the relationship between autophagy and cell death, as the association of autophagy with cell growth, nutrient utilization, survival and death indicates that this catabolic process is relevant to the treatment of many human disorders including cancer. (science20.com)
  • Under conditions such as stress or starvation, autophagy contributes to the breakdown of proteins and cellular compartments to generate amino acids required for the synthesis of proteins essential for cell survival. (biolegend.com)
  • By degrading cytoplasmic components autophagy releases amino acids for protein synthesis and fatty acids for oxidation in mitochondria to produce energy for survival. (sigmaaldrich.com)
  • Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly. (wikipedia.org)
  • Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. (elsevier.com)
  • The role of autophagy during cell death remains controversial but is important to our understanding and treatment of many human disorders including cancer and neurodegeneration," Baehrecke said. (science20.com)
  • At first glance, drugging autophagy sounds like a panacea, but each approach carries a risk: boosting autophagy might prevent neurodegeneration at the expense of increasing cancer risk, while inhibiting autophagy might kill cancer at the expense of the brain and other organs. (acs.org)
  • Autophagy concludes by the fusion of the autophagosome with the lysosome, where the cytoplasmic constituents are degraded by lysosomal hydrolases. (abcam.com)
  • 2012) while Bafilomycin A1 and chloroquine inhibit the autophagy by neutralizing the lysosomal pH and blocking autophagosome-lysosome fusion (see Fig. …. Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. (musicaenlamochila.net)
  • The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. (springer.com)
  • Finally, the work explores the relationship between autophagy and apoptosis, with attention to the ways in which autophagy regulates apoptosis, and the ways in which autophagy has been explored in Lepidoptera, elucidating the use of larval midgut as a model for such exploration. (elsevier.com)
  • mTORC1 regulates the downstream Atg1/Ulk1 autophagy-related kinase complex (11). (thefreelibrary.com)
  • Thus, a mitogen-activated protein kinase-dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles. (sciencemag.org)
  • Gene expression analysis further demonstrated that loss of endogenous Sirt1 inhibited autophagy, which regulates normal gland development. (wellnessresources.com)
  • To determine whether JFH-1-HCV infection regulates autophagy, we examined the conversion of endogenous LC3 to LC3 II. (pnas.org)
  • The counterpart of the yeast Apg12p conjugation system essential for autophagy. (springer.com)
  • Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. (springer.com)
  • The basic autophagy mechanism is conserved from yeast to man. (thefreelibrary.com)
  • The results suggest that the Sirt1 gene promotes autophagy and further highlight the role of the protein SIRT1 (the human homologue of the yeast Silent Information Regulator 2 (Sir2) gene) as a tumor suppressor in the prostate. (wellnessresources.com)
  • Autophagy requires the de novo formation of the nucleation complex, which in turn requires Beclin (Atg6 in yeast) to dissociate from its binding partner Bcl-2 ( 1 , 4 ) ( Fig. 1 ). (diabetesjournals.org)
  • In yeast, nutrient withdrawal is the primary stimulus that induces autophagy. (genome.jp)
  • BECN1, the ortholog of the yeast autophagy-related protein Atg6, is a critical component required for a lipid kinase complex involved in autophagy induction. (pubmedcentralcanada.ca)
  • Thus, autophagy is required for multiple roles in the prevention of human disease. (els.net)
  • In this review, we highlight the considerable progress made recently towards understanding the diverse roles of the cytoskeleton in autophagy. (nih.gov)
  • In addition to its physiological roles, autophagy also occurs in a wide variety of pathological processes, including tumour progression, metabolic disorders, and neurodegenerative and lung diseases. (royalsocietypublishing.org)
  • This clarifies the roles and relationships of three of the major features of neurodegenerative disease: aging, immunity, and autophagy," Giniger told Alzforum. (alzforum.org)
  • Recent findings now highlight roles for autophagy in mobilization of diverse cellular energy stores ( 4 ) and in adipocyte differentiation ( 5 , 6 ), thus presenting autophagy as an emerging player in the metabolic arena. (diabetesjournals.org)
  • Physiological roles of organelles autophagy in plant development and crop productivity. (frontiersin.org)
  • Autophagy is a fundamental eukaryotic process with multiple cytoplasmic homeostatic roles, recently expanded to include unique stand-alone immunological functions and interactions with nearly all parts of the immune system. (jimmunol.org)
  • In this article, we review this growing repertoire of autophagy roles in innate and adaptive immunity and inflammation. (jimmunol.org)
  • Physiological autophagy in the Syrian hamster Harderian gland / Ignacio Vega-Naredo and Ana Coto-Montes. (openlibrary.org)
  • Thanks to Ohsumi and others following in his footsteps, we now know that autophagy controls important physiological functions where cellular components need to be degraded and recycled," said the Nobel Foundation. (siliconrepublic.com)
  • In mammals, autophagy plays a vital role in maintenance of physiological steady state, biosynthesis of macromolecules, cellular development, tissue remodelling and adaptation to the environment [ 6 , 7 ]. (royalsocietypublishing.org)
  • The researchers were able to show that the complex plays an important role in autophagy, a physiological process that breaks down cellular proteins and organelles. (medindia.net)
  • These studies support the idea that the "housekeeping" role of autophagy, in fact, translates to key physiological functions. (diabetesjournals.org)
  • As novel functions for autophagy continue to unfold, it becomes critical to be able to precisely monitor autophagy in diverse physiological systems. (diabetesjournals.org)
  • Autophagy is generally activated by conditions of nutrient deprivation but has also been associated with physiological as well as pathological processes such as development, differentiation, neurodegenerative diseases, stress, infection, obesity, and cancer. (cellsignal.com)
  • These observations suggest that the primary physiological function of autophagy in neurons may not be to mobilize amino acids and other biosynthetic building blocks in response to starvation, in contrast to findings in other cell types. (jneurosci.org)
  • Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. (hindawi.com)
  • Dysregulated autophagy contributes to many pathologic processes including cancer and neurodegenerative diseases. (els.net)
  • This study suggests a potential role of autophagy in complement-associated processes that are associated with human diseases. (umassmed.edu)
  • Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging: Volume 9: Human Diseases and Autophagosome offers a valuable guide to both cellular processes while helping researchers explore their potentially important connections. (elsevier.com)
  • The role of autophagy in cancer-related processes is currently under investigation. (thefreelibrary.com)
  • In this regard, autophagy serves as an innate host defense mechanism, and some viruses and bacteria produce virulence factors that counteract these antimicrobial processes ( 4 - 7 ). (pnas.org)
  • Thus, the aim of this Research Topic is to extend our understanding of plant autophagy processes that degrade specific organelles during plant development. (frontiersin.org)
  • Relationship among autophagy and other processes for organelle turnover. (frontiersin.org)
  • Although typically considered to be degradative, autophagy also functions in homeostatic and even biosynthetic processes. (pubmedcentralcanada.ca)
  • The researchers trust that they will be able to impact autophagy processes in the future in order to treat various forms of cancer, neurodegenerative disorders, infectious diseases, and inflammatory reactions more effectively. (innovations-report.com)
  • Strikingly, this new strategy used by L. monocytogenes to avoid autophagy is independent of ActA, suggesting that InlK-MVP interactions and actin polymerization are two processes that favor the infection process in the same way. (pubmedcentralcanada.ca)
  • At the very least, autophagy under basal conditions could compromise the ability to respond optimally to fluctuations in blood glucose, posing a health risk. (sciencemag.org)
  • Though a basal or constitutive level of autophagy is present in almost all cell types all the time for elimination of damaged proteins and even dysfunctional organelles, for example, mitochondria, autophagy can be strongly induced to compensate for nutritional imbalances or in response to stresses such as DNA damage. (els.net)
  • Using live-cell imaging in mouse hippocampal neurons, we establish the compartment-specific mechanisms of constitutive autophagy under basal conditions, as well as in response to stress induced by nutrient deprivation. (jneurosci.org)
  • Autophagy occurs constitutively at a basal level, but is substantially induced by various stressors. (pubmedcentralcanada.ca)
  • This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity. (springer.com)
  • Pathogens and autophagy: Subverti. (mendeley.com)
  • Autophagy could be excessive or damaged organelles, such as mitochondria, invading pathogens, such as viruses or bacteria, or cytoplasmic macromolecules. (medindia.net)
  • In recent years, autophagy has been recognized to be also essential for several functions of innate and acquired immunity, e.g. antigen presentation and elimination of cytosolic pathogens. (fz-juelich.de)
  • Autophagy may engulf non-specific cell components, or selectively remove damaged components or invasive bacteria and other pathogens. (rxlist.com)
  • To counteract this mechanism, many pathogens have evolved to evade, subvert, or exploit autophagy. (pnas.org)
  • B) Alternatively, autophagy can sequester cytosolic proteins such as ubiquitin and ribosomal proteins (pear-shaped tan-colored shapes, ribosomes) and digest them into antimicrobial peptides (AMPs) that can be delivered to pathogens confined in phagosomes. (jimmunol.org)
  • In crinophagy (the least well-known and researched form of autophagy), unnecessary secretory granules are degraded and recycled. (wikipedia.org)
  • A novel form of autophagy identified in primary rat hepatocytes. (uio.no)
  • Substrate proteins are unfolded prior to their internalization, which is not required in other forms of autophagy. (sigmaaldrich.com)
  • In recent years, a growing body of evidence has shown that autophagy also plays a key role in the development of mammalian diseases, a function that has garnered substantial attention and study. (royalsocietypublishing.org)
  • Increasing evidence has shown that autophagy dysfunction is related to several pathologies including neurodegenerative diseases and cancer. (scielo.br)
  • The class III type phosphoinositide 3-kinase (PI3K class III or hVps34) is a major regulator of autophagy. (cellsignal.com)
  • The amino acid leucine , which is contained in nearly all proteins, is also a key regulator of autophagy. (care2.com)
  • wherein optionally the protein comprises or consists of a Tat-Atg5K130R (Tat-Atg5 K130R ) (inhibitor of autophagy), a Tat-Beclin 1 (stimulates or increases autophagy), or a peptidomimetic or synthetic form thereof, or an equivalent thereof. (freepatentsonline.com)
  • The coaddition of ERβ agonist and the autophagy inhibitor chloroquine resulted in a significant accumulation of sub-G 1 DNA which was completely prevented by the addition of the caspase inhibitor Z-VAD-FMK.Wepropose that combined therapies with anERb agonist and an inhibitor of autophagy may provide the basis for a novel approach to the. (musicaenlamochila.net)
  • There is also a link between programmed cell death like apoptosis and autophagy. (news-medical.net)
  • Treatment with melittin induces apoptosis and autophagy of fibroblastlike synoviocytes in patients with rheumatoid arthritis. (greenmedinfo.com)
  • Explores the role of autophagy in specific diseases and developments, including: Crohn's Disease, Gaucher Disease, Huntington's Disease, HCV infection, osteoarthritis, and liver injury, with a full section devoted to in-depth exploration of autophagy in tumor development and cancer, as well as the relationship between autophagy and apoptosis. (elsevier.com)
  • This review had the purpose of discussing the issue to confirm whether a relationship between autophagy dysfunction and osteoporosis exits. (scielo.br)
  • Here, we discuss the probable cause and effect relationship between perturbed autophagy and aging, as well as possible molecular mechanisms that may mediate the anti-aging effects of autophagy. (nih.gov)
  • Klionsky DJ (2005) The molecular machinery of autophagy: unanswered questions. (springer.com)
  • This extracellular molecular link raises the possibility that the breakdown between an immune system signal and autophagy could contribute to human diseases. (umassmed.edu)
  • Work is underway to elucidate molecular mechanisms of autophagy in heart and to explore its contribution to the pathogenesis of heart failure. (utsouthwestern.edu)
  • An in-depth understanding of the molecular role that autophagy plays in pathological settings is vital for both the diagnosis and treatment of mammalian diseases and will aid in the search for novel targets for therapeutic drug intervention. (royalsocietypublishing.org)
  • Thus the molecular description of autophagy is a relatively recent phenomenon (Klionsky and Emr, 2000). (rupress.org)
  • The goal of the new research center is a better understanding of autophagy at the molecular and cellular level. (innovations-report.com)
  • Within the new collaborative research center, scientists are planning to investigate autophagy at the molecular, cellular, and model organism level. (innovations-report.com)
  • A double membrane surrounds organelles such as mitochondria (A) during autophagy. (rupress.org)
  • Removal of damaged mitochondria by autophagy is called mitophagy, which is triggered by accumulation of activated PINK1 at the mitochondrial membrane. (biolegend.com)
  • In addition, stress-induced autophagy has been linked to several diseases, one of them being cancer. (mcponline.org)
  • In order to specifically examine the role of stress-induced autophagy in exercise, He et al. (pubmedcentralcanada.ca)
  • Autophagy is recognized as the main tool to degrade damaged organelles and misfolded proteins. (slideshare.net)
  • 1. 1Cardiovascular Research Focus www.ptglab.com AUTOPHAGY RESEARCH FOCUS www.ptglab.com Autophagy is recognized as the main tool to degrade damaged organelles and misfolded proteins. (slideshare.net)
  • But by flipping the ATG8 protein 180°, scientists based at Washington University in St. Louis have discovered a whole new set of receptors that can draw cellular wallflowers-poorly folded proteins and dysfunctional organelles-into the autophagy dance. (genengnews.com)
  • During autophagy, a semicircular membrane known as phagophore forms and closes around some of the molecules and organelles in the cytoplasm and becomes what is known as an autophagosome. (rxlist.com)
  • Autophagy is the destructive process in which a double membrane envelops cytoplasm and organelles before targeting them to lysosomes for destruction. (rupress.org)
  • Autophagy is a dynamic cellular recycling system that degrades cytoplasmic contents, abnormal protein aggregates, and excess or damaged organelles so that the building blocks, such as amino acids, can be used to create new cellular components. (cellsignal.com)
  • A primary and unique function of autophagy is to degrade entire organelles, which can be used to recycle cell components and generate energy. (biolegend.com)
  • Autophagy is unique in its capacity to sequester, remove, or process bulk cytosol, cytoplasmic organelles ( 1 ), invading microbes, and immunological mediators ( 2 ), as depicted in Fig. 1 . (jimmunol.org)
  • B) As a topological inverter device, autophagy can deliver cytosolic PAMPs to the lumen of endomembranous organelles, where they can interact with the receptor portions of TLRs. (jimmunol.org)
  • Autophagy is generally considered to be a cytoprotective response to stress, whether in the form of nutrient deprivation or the presence of dysfunctional organelles. (pubmedcentralcanada.ca)
  • The ULK1/2 kinase complex initiates autophagy when mTORC1 inactivation interrupts the inhibitory phosphorylation of ULK1/2. (els.net)
  • In the presence of growth signals, TOR kinase suppresses autophagy initiation by inhibiting a kinase complex containing ATG17 . (biolegend.com)
  • During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. (ebi.ac.uk)
  • Autophagy, which literally translates into "eating one's own self," is an evolutionarily conserved cellular recycling program that maintains "in-house" quality control by turning over cytoplasmic components within lysosomes ( 1 ). (diabetesjournals.org)
  • Example of IC data by Autophagy Watch Starvation induces increasing the amount of LC3-II. (musicaenlamochila.net)
  • In this review, experts describe how autophagy, the cellular process responsible for clearing old or damaged parts of the cell, plays a critical role supporting synaptic maintenance in the healthy brain, and how autophagy dysfunction in HD may thereby lead to impaired synaptic maintenance and thus early manifestations of disease. (eurekalert.org)
  • Autophagy may refer to: Autophagy (cellular process), a process in cellular biology Autophagia, a mental disorder or a symptom of a mental disorder Autophagy (journal), a scientific journal Self-cannibalism This disambiguation page lists articles associated with the title Autophagy. (wikipedia.org)
  • Autophagy is an important cellular process that is involved in energy production, cellular stress response, and immune reactions. (innovations-report.com)
  • He had just joined the life sciences-based venture capital firm Third Rock Ventures, and the investors there were building a company centered on the cellular process of autophagy, the subject of the 2016 Nobel Prize in Physiology or Medicine , announced just months before. (acs.org)
  • Autophagy is a catabolic process. (rxlist.com)
  • Autophagy is a cellular catabolic process that relies on the cooperation of autophagosomes and lysosomes. (sciencemag.org)
  • While apoptosis is the most understood type of programmed cell death, recently scientists have begun to take a closer look at autophagy- a highly regulated, catabolic process that essentially allows a cell to eat itself. (science20.com)
  • This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome. (nature.com)
  • However, these experimental results do not directly demonstrate that defects in autophagy contribute to pathogenesis of human diseases. (nature.com)
  • Thus, it has become particularly important to understand the genetic basis of putative human autophagy-related diseases. (nature.com)
  • Dysfunctions in autophagy would cause a variety of illnesses including cancer, inflammatory bowel disease and neurodegenerative diseases. (springer.com)
  • As hepatic fibrosis is a common outcome of a variety of chronic liver diseases, this review will highlight and summarize recent progresses of the role of autophagy in hepatic fibrosis. (hindawi.com)
  • In this Review, we consider how certain neurodegenerative diseases may be associated with impaired autophagy and how this may affect pathology. (jci.org)
  • While these misfolded proteins may cause pathology via diverse mechanisms, in recent years there has been a focus on the role of autophagy in these diseases, both as a pathologic mechanism and as a therapeutic target. (jci.org)
  • In this Review we discuss the evidence that a disruption in autophagy might be a contributing factor in aggregate formation and the progression of neurodegenerative diseases. (jci.org)
  • Deregulation of autophagy has been implicated in a number of severe human diseases, in particular neurodegenerative disorders and neoplasias. (fz-juelich.de)
  • Volume 9 emphasizes the role of autophagy in diseases, such as leukemia, antifungal and antibacterial immunity, and transplantation. (elsevier.com)
  • Aberrations in autophagy are associated with several diseases, including cancer. (mdpi.com)
  • Abnormalities related to autophagy are known to be related to various human pathologies ranging from neurodegenerative diseases to cancer, including hepatocellular carcinoma (HCC) (5). (thefreelibrary.com)
  • On the other hand, autophagy is related to several liver diseases, including fatty liver disease and HCC (7,8). (thefreelibrary.com)
  • Several other studies have shown links between autophagy defects, aging and degenerative diseases like Parkinson s, Alzheimer s and even cancer ( 2 , 3 , 4 ). (care2.com)
  • At the 11th International Conference on Alzheimer's and Parkinson's Diseases, held 6-10 March 2013 in Florence, Italy, researchers intrigued the crowd with compelling evidence for an inflammatory role, strengthened evidence that LRRK2 affects endocytosis and autophagy, and pointed to kinase activity as a plausible target for intervention. (alzforum.org)
  • Autophagy plays a key role in human physiology, and its dysregulation is implicated in many diseases. (uio.no)
  • During autophagy, a nascent, double-membrane-bound vesicle called an autophagosome sequesters and transports a portion of cytoplasm into the vacuolar lumen for digestion. (frontiersin.org)
  • Autophagy occurs when the protein, organelle, or cytoplasmic content to be degraded is surrounded by a small portion of membrane, creating an autophagosome. (cellsignal.com)
  • The morphological hallmark of autophagy is the formation of a double-membrane cytosolic vesicle, the autophagosome, which sequesters cytoplasm and delivers it to the lysosome where it is degraded and recycled. (pubmedcentralcanada.ca)
  • The process of autophagy has been conserved over time among all living organisms. (news-medical.net)
  • As the signals for autophagy are in place and there is induction of the process, the next step is to select the material that is to be removed or broken down. (news-medical.net)
  • Retrieved on January 27, 2020 from https://www.news-medical.net/health/Autophagy-Process.aspx. (news-medical.net)
  • When there is starvation or nutrient deprivation, the process of autophagy is triggered. (news-medical.net)
  • Half a century ago, Christian de Duve coined the term "autophagy" (literally, "self-eating" in Greek) to describe a process where the cell digests its cytoplasmic materials within lysosomes 1 . (nature.com)
  • Mizushima N (2007) Autophagy: process and function. (springer.com)
  • Autophagy is a powerful process for removing such proteins. (jci.org)
  • The 2016 Nobel Prize winner for physiology or medicine is Yoshinori Ohsumi, for his 1990s work on autophagy, discovering the mechanism behind the process. (siliconrepublic.com)
  • The process of autophagy can be broken down into a series of sequential stages ( figure 1 ). (royalsocietypublishing.org)
  • What is the process of autophagy? (rxlist.com)
  • Autophagy is a natural process that occurs all the time in the cell, less when well-fed, and more when under stress. (rxlist.com)
  • Protein kinases are integral to the autophagy process. (mdpi.com)
  • While fasting is definitely a useful tool to keep in your health-kit, it's not the only way to increase the autophagy process. (robbwolf.com)
  • This automatic process is called autophagy and it works when the body is in a fasted state. (care2.com)
  • SIGNIFICANCE STATEMENT Autophagy is an essential homeostatic process in neurons, but neuron-specific mechanisms are poorly understood. (jneurosci.org)
  • Axonal autophagy is a vectorial process that delivers cargo from the distal axon to the soma. (jneurosci.org)
  • Collectively, the unique features of autophagy as an immunological process and its contributions to other arms of the immune system represent a new immunological paradigm. (jimmunol.org)
  • Recent reviews provide a more comprehensive introduction to autophagy and reagents that affect the process ( 2 , 7 ). (jimmunol.org)
  • Therefore, autophagy is fundamental for the maintenance of cell viability, acting as a quality control process that prevents the accumulation of unnecessary structures and oxidative stress. (scielo.br)
  • As demonstrated by the 2016 Nobel Prize winner, Yoshinori Ohsumi , autophagy is a fundamental process vital to cellular health. (horizondiscovery.com)
  • Autophagy is a highly regulated process that is involved in cell growth, development, and death. (sigmaaldrich.com)
  • The process of autophagy can be divided into several phases. (sigmaaldrich.com)
  • We conclude that autophagy, an inherent cellular response process, is triggered by the cellular uptake of CPP-based transfection system. (sigmaaldrich.com)
  • Autophagy represents an extremely complex and precisely regulated process that depends on the coordination of many players. (innovations-report.com)
  • It has long been thought that autophagy represents an unspecific process. (innovations-report.com)
  • Autophagy, the cellular equivalent of housecleaning, is now recognized as a crucial process of self-renewal. (acs.org)
  • Autophagy is an essential, homeostatic process by which cytoplasmic materials are degraded in lysosomes. (invivogen.com)
  • Role in cellular stress - autophagy is a response to cellular stress. (news-medical.net)
  • Embryonic development - autophagy plays an important role in development of the embryo by maintain a critical balance of energy levels and sources. (news-medical.net)
  • This short review discusses and summarizes this correlation with a focus on the possible role of autophagy and mechanisms in it. (springer.com)
  • Recent evidence indicates that autophagy plays a central role in synaptic maintenance, and the disruption in autophagy may be at the root of these early cognitive changes. (eurekalert.org)
  • We have long thought that autophagy played a role in the pathophysiology of HD, but what this role is has been unclear until recently. (eurekalert.org)
  • Autophagy plays a specialized role in the maintenance and function of the synapse, and mHtt may disrupt this function, leading to the early synaptic changes seen in HD patients and model systems," explained Dr. Grosso Jasutkar. (eurekalert.org)
  • however, the role of autophagy in retinal degeneration has remained unclear. (mendeley.com)
  • Additionally, the Psd knockdown-induced retinal degeneration phenotype was enhanced by Ppt1 inactivation, which causes infantile neuronal ceroid lipofuscinosis, implying that autophagy plays a significant role in its pathogenesis. (mendeley.com)
  • Analysis of a subset also harboring ubiquitin regulatory X (UBX) domains revealed a role for UIM-directed autophagy in clearing nonfunctional CDC48/p97 complexes, including some impaired in human disease," the article detailed. (genengnews.com)
  • This volume also includes an explanation of the role of the autophagy-related gene ATG5 in cancer (e.g., gastrointestinal cancer). (elsevier.com)
  • The current study aimed to investigate the occurrence of autophagy in the developing mouse lung and its regulatory role in airway branching and terminal sacculi formation. (jci.org)
  • These results illustrate a previously unappreciated role for autophagy in the establishment of a viral infection and they suggest that different host factors regulate the translation of incoming viral genome and translation of progeny HCV RNA once replication is established. (pnas.org)
  • How these potentially anti-aging results are achieved is also still in question, but in addition to oxidation defense and upregulation of cell metabolism, it appears that autophagy plays a major role. (abovetopsecret.com)
  • Additionally, autophagy was inhibited using 3methyladenine (3MA) and beclin1 ablation, to determine its role in 5FUmediated cell death. (ingentaconnect.com)
  • Role of autophagy in cell-penetrating peptide transfection model. (sigmaaldrich.com)
  • We have a particular interest in the role of autophagy in cancer. (uio.no)
  • ActA is a surface protein produced by L. monocytogenes to polymerize actin and mediate intra- and intercellular movements, which plays a critical role in autophagy escape. (pubmedcentralcanada.ca)
  • Understanding the role of MVP may provide new insights into bacterial infection and autophagy. (pubmedcentralcanada.ca)
  • While the role of ActA in autophagy is now well established, the role of many other surface proteins during Listeria infection remains elusive. (pubmedcentralcanada.ca)
  • In 1999, a landmark discovery connecting autophagy with cancer was published by Beth Levine's group. (wikipedia.org)
  • [24] To this date, relationship between cancer and autophagy continues to be a main theme of autophagy research. (wikipedia.org)
  • Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy. (springer.com)
  • The remaining chapters will cover topics on autophagy and cancer therapy. (springer.com)
  • Dr. Wang is a leading research scientist in the area of autophagy and cancer. (springer.com)
  • A full section is devoted to in-depth exploration of autophagy in tumor development and cancer. (elsevier.com)
  • Autophagy and liver cancer. (thefreelibrary.com)
  • S.v. Autophagy and liver cancer. (thefreelibrary.com)
  • During the early phase of cancer development when tumors have not yet gained access to the blood system and thus have to survive in a nutrient-limited environment, autophagy may act as a prosurvival mechanism securing cellular energy needs ( 13 , 14 ). (mcponline.org)
  • Intersections between autophagy and apoptosis under ER stress conditions, and mechanisms of cell death induced by therapeutically relevant anti-cancer drugs. (uio.no)
  • Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM (2006) In Situ Detection of Starvation-induced Autophagy. (springer.com)
  • We studied global protein dynamics during amino acid starvation-induced autophagy by quantitative mass spectrometry and were able to record nearly 1500 protein profiles during 36 h of starvation. (mcponline.org)
  • Although the discovery of lysosomes dates back to the 1950s through the electron microscopic work of Christian De Duve, recent years have seen a growing interest in autophagy research, and reports now link compromised autophagy to a wide array of common human pathologies, for instance, neurodegenerative disorders, metabolic alterations, microbial pathogenesis, and cancers, to mention just a few ( 2 ). (diabetesjournals.org)
  • Autophagy in Neurons. (nih.gov)
  • The article could shed light on why autophagy sometimes fails, allowing defective cellular material to accumulate and contribute to disorders such as Huntington's disease, Alzheimer's, Parkinson's disease, and Lou Gehrig's Disease/ALS, where this trash blocks neurons from transmitting signals. (genengnews.com)
  • The scientists traced the cause to weakened autophagy in neurons, which in turn unleashed a massive inflammatory response that accelerated age-related neuron loss. (alzforum.org)
  • Restoring autophagy or inflammation to normal saved neurons. (alzforum.org)
  • When they stimulated autophagy in the flies, neurons made fewer AMPs and more dopaminergic neurons survived. (alzforum.org)
  • There is a cascade where defective autophagy hyperstimulates immunity, hyperimmunity kills neurons, and this specific insult acts synergistically with the general fragility of aging to produce the overall effects of disease," he proposed. (alzforum.org)
  • Initial observations suggest that autophagy is spatially regulated in neurons, but how autophagy is regulated in distinct neuronal compartments is unclear. (jneurosci.org)
  • While starvation robustly decreased mTORC1 signaling in neurons, this decrease was not sufficient to activate autophagy. (jneurosci.org)
  • Autophagy has certain links with a variety of causes of hippocampal neuronal injury. (springer.com)
  • The current correlation between autophagy and hippocampal neuronal injury has not been completely determined by the general public alike. (springer.com)
  • Further studies are needed to determine special effects of autophagy on hippocampal neuronal injury, which might accelerate the development of therapeutic interventions in hippocampal neuronal injury in many neurological disorders. (springer.com)
  • Nixon RA, Yang DS (2012) Autophagy and neuronal cell death in neurological disorders. (springer.com)
  • Thus, decreasing autophagy appears to prevent neuronal degeneration The LC3 Antibody Kit for Autophagy includes a rabbit polyclonal antibody against LC3B that has been validated for use in fluorescence microscopy and high content imaging and analysis. (musicaenlamochila.net)
  • Reggiori F, klionsky DJ (2002) Autophagy in the eukaryotic cell. (springer.com)
  • Perinuclear aggresome formation is a key mechanism to dispose of misfolded proteins that exceed the degradative capacity of ubiquitin-proteasome and autophagy-lysosome systems. (pnas.org)
  • With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future. (hindawi.com)
  • The most well known mechanism of autophagy involves the formation of a membrane around a targeted region of the cell, separating the contents from the rest of the cytoplasm . (fightaging.org)
  • This also indicates that autophagy might be involved in degrading cell structures after death related proteases are activated. (news-medical.net)
  • Recent evidence indicates that autophagy may be important in maintaining the synapse. (eurekalert.org)
  • Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. (springer.com)
  • Ascorbic acid significantly decreased the cerebral damage, reduced oxidative stress and inhibited autophagy by reducing de novo synthesis of beclin 1. (greenmedinfo.com)
  • Classic autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) can inhibit lung and colon cancers and thus have potential for tumor treatment [16-18]. (musicaenlamochila.net)
  • Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. (springer.com)
  • show a direct and nutrient-sensitive interaction between the tumor suppressor p53 and the essential autophagy gene Atg7. (sciencemag.org)
  • When the autophagy protein Atg7 is absent, nutrient withdrawal does not stop the cell cycle. (sciencemag.org)