AnatomyDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceGeographicals
AutophagyPhagosomesMicrotubule-Associated ProteinsApoptosis Regulatory ProteinsLysosomesUbiquitin-Activating EnzymesTOR Serine-Threonine KinasesClass III Phosphatidylinositol 3-KinasesVacuolesAdenineApoptosisLysosomal-Associated Membrane Protein 2Models, BiologicalSignal TransductionCell Line, TumorSirolimusMembrane ProteinsMitochondrial DegradationCell SurvivalChloroquineMicroscopy, Electron, TransmissionProteolysisCell DeathRNA, Small InterferingMitochondriaEndoplasmic Reticulum StressRNA InterferenceReactive Oxygen SpeciesGene Knockdown TechniquesMultiprotein ComplexesCytoprotectionStarvationNeurodegenerative DiseasesCell LineUbiquitinAdaptor Proteins, Signal TransducingProteasome Endopeptidase ComplexAMP-Activated Protein KinasesStress, PhysiologicalGreen Fluorescent ProteinsEncyclopedias as TopicCytoplasmGermanyOrganellesGlucagon-Like Peptide 2PubMedPeriodicals as TopicBooksPublishingMEDLINESerial Publications
Autophagy: 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.Phagosomes: 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.Microtubule-Associated Proteins: 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.Apoptosis Regulatory Proteins: 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.Lysosomes: 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)Ubiquitin-Activating Enzymes: 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.TOR Serine-Threonine Kinases: 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.Class III Phosphatidylinositol 3-Kinases: 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.Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Apoptosis: 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.Lysosomal-Associated Membrane Protein 2: 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.Models, Biological: 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.Signal Transduction: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Sirolimus: 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.Membrane Proteins: 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.Mitochondrial Degradation: Proteolytic breakdown of the MITOCHONDRIA.Cell Survival: 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.Chloroquine: 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.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Proteolysis: 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.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.RNA, Small Interfering: 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.Mitochondria: 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)Endoplasmic Reticulum Stress: 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.RNA Interference: 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.Reactive Oxygen Species: 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.Gene Knockdown Techniques: 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.Multiprotein Complexes: Macromolecular complexes formed from the association of defined protein subunits.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Starvation: Lengthy and continuous deprivation of food. (Stedman, 25th ed)Neurodegenerative Diseases: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Ubiquitin: 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.Adaptor Proteins, Signal Transducing: 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 enzymesProteasome Endopeptidase Complex: 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.AMP-Activated Protein Kinases: 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.Stress, Physiological: 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.Green Fluorescent Proteins: 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.Encyclopedias as Topic: 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)Cytoplasm: 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)GermanyOrganelles: 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.Glucagon-Like Peptide 2: A 33-amino acid peptide derived from the C-terminal of PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. It stimulates intestinal mucosal growth and decreased apoptosis of ENTEROCYTES. GLP-2 enhances gastrointestinal function and plays an important role in nutrient homeostasis.PubMed: 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.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.BooksPublishing: "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.MEDLINE: 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).Serial Publications: 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)

Autophagy Flux ChloroquineAutophagy Flux Chloroquine
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 ...
Uba1 functions in Atg7- and Atg3-independent autophagy by Tsun-Kai Chang, Bhupendra V. Shravage et al."Uba1 functions in Atg7- and Atg3-independent autophagy" by Tsun-Kai Chang, Bhupendra V. Shravage et al.
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.
Aging | Prognostic implications of autophagy-associated gene signatures in non-small cell lung cancer - Full TextAging | Prognostic implications of autophagy-associated gene signatures in non-small cell lung cancer - Full Text
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
北京大学医学部机构知识库(IR@PKUHSC): Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal...北京大学医学部机构知识库([email protected]): Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal...
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 ...
Autophagy modulators - Pipeline Insights, 2017 | HealthcareAutophagy modulators - Pipeline Insights, 2017 | Healthcare
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 ...
The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation. - The Kennedy...The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation. - The Kennedy...
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
Cells | Free Full-Text | The Selectivity and Specificity of Autophagy in DrosophilaCells | Free Full-Text | The Selectivity and Specificity of Autophagy in Drosophila
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
A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells. - Oxford...A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells. - Oxford...
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
Cells | Free Full-Text | Assays to Monitor Autophagy in Saccharomyces cerevisiaeCells | Free Full-Text | Assays to Monitor Autophagy in Saccharomyces cerevisiae
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
Lack of autophagy in the hematopoietic system leads to loss of hematopoietic stem cell function and dysregulated myeloid...Lack of autophagy in the hematopoietic system leads to loss of hematopoietic stem cell function and dysregulated myeloid...
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).
Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensin II-exposed cardiomyocytes ...Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensin II-exposed cardiomyocytes ...
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 ...
Plus itPlus it
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 ...
TBK1 Mediates Cross-Talk Between the Innate Immune Response and Autophagy | Science SignalingTBK1 Mediates Cross-Talk Between the Innate Immune Response and Autophagy | Science Signaling
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 ...
Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging. - Nuffield Department of Orthopaedics...Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging. - Nuffield Department of Orthopaedics...
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
Autophagy Regulation Chapter 98 : The Guide - Mangakakalot.comAutophagy Regulation Chapter 98 : The Guide - Mangakakalot.com
Read Autophagy Regulation chapter 98 : The Guide online free and high quality at Mangakakalot.com. Fast loading speed, unique reading type: All pages - just need to scroll to read next page
Frontiers | Increased Interleukin-23 in Hashimotos Thyroiditis Disease Induces Autophagy Suppression and Reactive Oxygen...Frontiers | Increased Interleukin-23 in Hashimoto's Thyroiditis Disease Induces Autophagy Suppression and Reactive Oxygen...
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.
British Library EThOS: Characterisation of mammalian Atg9 and its role in autophagyBritish Library EThOS: Characterisation of mammalian Atg9 and its role in autophagy
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, ...
INVESTIGATING THE ROLE OF CELLULAR AUTOPHAGY IN HUMAN MONOCYTIC CELL DEATH BY KINOME ANALYSISINVESTIGATING THE ROLE OF CELLULAR AUTOPHAGY IN HUMAN MONOCYTIC CELL DEATH BY KINOME ANALYSIS
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, PhDAutophagy (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 ...
Absence of altered autophagy after myocardial ischemia in diabetic compared with nondiabetic mice. - Semantic ScholarAbsence of altered autophagy after myocardial ischemia in diabetic compared with nondiabetic mice. - Semantic Scholar
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
Autophagy - Adaptive Molecular Mechanisms in Condition of StarvationAutophagy - Adaptive Molecular Mechanisms in Condition of Starvation
|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|
Leishmania donovani Induces Autophagy in Human Blood-Derived Neutrophils - Espace INRSLeishmania donovani Induces Autophagy in Human Blood-Derived Neutrophils - Espace INRS
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 ...
Presenilin Is Necessary for Efficient Proteolysis through the Autophagy-Lysosome System in a γ-Secretase-Independent Manner |...Presenilin Is Necessary for Efficient Proteolysis through the Autophagy-Lysosome System in a γ-Secretase-Independent Manner |...
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 ...
Nrf2-Mediated Cardiac Maladaptive Remodeling and Dysfunction in a Setting of Autophagy Insufficiency | HypertensionNrf2-Mediated Cardiac Maladaptive Remodeling and Dysfunction in a Setting of Autophagy Insufficiency | Hypertension
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 ...
NBR1-Mediated Selective Autophagy Targets Insoluble Ubiquitinated Protein Aggregates in Plant Stress ResponsesNBR1-Mediated Selective Autophagy Targets Insoluble Ubiquitinated Protein Aggregates in Plant Stress Responses
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
Autophagy is considered a cytoprotective function in cancer therapy under certain conditions and is a drug resistance mechanism...Autophagy is considered a cytoprotective function in cancer therapy under certain conditions and is a drug resistance mechanism...
Autophagy is considered a cytoprotective function in cancer therapy under certain conditions and is a drug resistance mechanism that represents a clinical obstacle to successful cancer treatment and leads to poor prognosis in cancer patients. and development of targeting cytoprotective autophagy as a cancer therapeutic approach in clinical application. Thus, we need to facilitate the exploitation of appropriate autophagy inhibitors and coadministration delivery system to cooperate with anticancer drugs. This review aims to note optimal combination strategies by modulating autophagy for therapeutic advantage to overcome drug resistance and enhance the effect of antitumor therapies on cancer patients. genomic interference against autophagic genes (siRNA targeting Atg3, Atg5, Atg7, and Beclin 1) or pharmacological inhibitors of key components within the autophagy pathway in cancer resistance (Kumar et al., 2015) (Table 1). Additionally, there is also a growing interest in exploring more potent and ...
Autophagy in neuroinflammatory diseases. | UnivOAKAutophagy in neuroinflammatory diseases. | UnivOAK
Show moreAutophagy is a metabolically-central process that is crucial in diverse areas of cell physiology. It ensures a fair balance between life and death molecular and cellular flows, and any disruption in this vital intracellular pathway can have consequences leading to major diseases such as cancer, metabolic and neurodegenerative disorders, and cardiovascular and pulmonary diseases. Recent pharmacological studies have shown evidence that small molecules and peptides able to activate or inhibit autophagy might be valuable therapeutic agents by down- or up-regulating excessive or defective autophagy, or to modulate normal autophagy to allow other drugs to repair some cell alteration or destroy some cell subsets (e.g. in the case of cancer concurrent treatments). Here, we provide an overview of neuronal autophagy and of its potential implication in some inflammatory diseases of central and peripheral nervous systems. Based on our own studies centred on a peptide called P140 that targets ...
Autophagy: Cancer, Other Pathologies, Inflammation, by M. A. Hayat | Antonio Ceballos BooksAutophagy: Cancer, Other Pathologies, Inflammation, by M. A. Hayat | Antonio Ceballos Books
By M. A. Hayat. Understanding the significance and necessity of the function of autophagy in health and wellbeing and ailment is key for the stories of melanoma, getting older, neurodegeneration, immunology, and infectious illnesses. complete and updated, this publication deals a worthwhile consultant to those mobile approaches when inciting researchers to discover their almost certainly very important connections. Volume 7 presents assurance of the newest advancements in autophagosome biogenesis and rules; the position of autophagy in protein quality controls; and the function of autophagy in apoptosis. awareness is given to autophagy within the cardiovascular method, with specific insights into the function of autophagy in atherosclerosis and the particular habit of autophagy within the sinoatrial node. state of the art findings within the relationships among autophagy and way of life are explored with the law of macroautophagy in keeping with workout, in addition to the promoting of ...
DGIST Scholar: Autophagy for the quality control of adult hippocampal neural stem cellsDGIST Scholar: Autophagy for the quality control of adult hippocampal neural stem cells
Autophagy plays an important role in neurodegeneration, as well as in normal brain development and function. Recent studies have also implicated autophagy in the regulation of stemness and neurogenesis in neural stem cells (NSCs). However, little is known regarding the roles of autophagy in NSC biology. It has been shown that in addition to cytoprotective roles of autophagy, pro-death autophagy, or ׳autophagic cell death (ACD), regulates the quantity of adult NSCs. A tight regulation of survival and death of NSCs residing in the neurogenic niches through programmed cell death (PCD) is critical for maintenance of adult neurogenesis. ACD plays a primary role in the death of adult hippocampal neural stem (HCN) cells following insulin withdrawal. Despite the normal apoptotic capability of HCN cells, they are committed to death by autophagy following insulin withdrawal, suggesting the existence of a unique regulatory program that controls the mode of cell death. We propose that dual roles of ...
CEF-MC : Roles of autophagy during tumorigenesisCEF-MC : Roles of autophagy during tumorigenesis
January 2016. Autophagy can act either as a tumor suppressor or as a survival mechanism for established tumors. To understand how autophagy plays this dual role in cancer, in vivo models are required. By using a highly heterogeneous C. elegans germline tumor, the research group of Christian Pohl in collaboration with the research group of Ivan Dikic could now show that autophagy-related proteins are expressed in a specific subset of tumor cells, the neurons. Moreover, they could demonstrate that inhibition of autophagy impairs neuronal differentiation and results in a shorter life span of animals with tumors. In contrast, induction of autophagy extends life span by impairing tumor proliferation, which also depends on modular changes in transcription networks and mitochondrial metabolism. The findings from this work, recently published in the journal Autophagy, suggest that metabolic restructuring, cell-type specific regulation of autophagy and neuronal differentiation play key roles in ...
Selective degradation of PU.1 during autophagy represses the differentiation and antitumour activity of TH9 cellsSelective degradation of PU.1 during autophagy represses the differentiation and antitumour activity of TH9 cells
Autophagy, a catabolic mechanism that involves degradation of cellular components, is essential for cell homeostasis. Although autophagy favours the lineage stability of regulatory T cells, the contribution of autophagy to the differentiation of effector CD4 T cells remains unclear. Here we show that autophagy selectively represses T helper 9 (TH9) cell differentiation. CD4 T cells lacking Atg3 or Atg5 have increased interleukin-9 (IL-9) expression upon differentiation into TH9 cells relative to Atg3- or Atg5-expressing control cells. In addition, the TH9 cell transcription factor, PU.1, undergoes K63 ubiquitination and degradation through p62-dependent selective autophagy. Finally, the blockade of autophagy enhances TH9 cell anticancer functions in vivo, and mice with T cell-specific deletion of Atg5 have reduced tumour outgrowth in an IL-9-dependent manner. Overall, our findings reveal an unexpected function of autophagy in the modulation of TH9 cell differentiation and antitumour activity, and prompt
Most recent papers with the keyword Septin | Read by QxMDMost recent papers with the keyword Septin | Read by QxMD
Autophagy is a conserved cellular degradation pathway wherein double-membrane vesicle called autophagosomes capture long-lived proteins and damaged or superfluous organelles and deliver them to the lysosome for degradation. Septins are conserved GTP-binding proteins involved in many cellular processes, including phagocytosis and autophagy of intracellular bacteria, but no role in general autophagy was known. In budding yeast, septins polymerize into ring-shaped arrays of filaments required for cytokinesis. In an unbiased genetic screen and in subsequent targeted analysis, we found autophagy defects in septin mutants, and co-localized septins in rings at the pre-autophagosomal structure (PAS) and on autophagosomes where they physically interact with the autophagy proteins Atg8 and Atg9 ...
The autophagy machinery restrains iNKT cell activation through CD1D1 internalization. | Physicians Weekly for Medical News,...The autophagy machinery restrains iNKT cell activation through CD1D1 internalization. | Physician's Weekly for Medical News,...
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT-cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II containing compartments (MIICs) before recycling to the plasma membrane. Autophagosomes intersect with MIICs and autophagy-related proteins are known to support antigen loading for increased CD4(+) T cell immunity. Here, we report that mice with dendritic cell (DC)-specific deletion of the essential autophagy gene Atg5 showed better CD1D1-restricted glycolipid presentation in vivo. These effects led to enhanced iNKT cell cytokine production upon antigen recognition and lower bacterial loads ...
Functions of autophagy in lipid homeostasis and survival in androgen-d by Ramesh Kaini"Functions of autophagy in lipid homeostasis and survival in androgen-d" by Ramesh Kaini
Androgen deprivation therapy, one of the standard treatments for prostate cancer, induces apoptosis as well as autophagy in androgen-responsive PCa cells. As modulation of autophagy is a new paradigm for enhancing the therapeutic efficacy of various cancer therapies, we sought to determine the functions of autophagy during androgen deprivation. In this study, we confirmed that androgen removal or inhibition induces autophagy in two different hormone sensitive prostate cancer cells. Androgen deprivation also caused depletion of lipid droplets which was abrogated on inhibition of autophagy by pharmacological means (3-methyladenine, bafilomycin A1) or using a genetic approach (Atg5 siRNA). In addition, colocalization of lipid droplets and autophagic vesicles was observed in LNCaP cells, which was further enhanced by blocking the autophagic flux. These findings suggest that autophagy mediates lipid droplet degradation and lipolysis in androgen sensitive prostate cancer cells. Furthermore, inhibition of
Inhibition of protein synthesis separates autophagic sequestration from the delivery of lysosomal enzymes | Journal of Cell...Inhibition of protein synthesis separates autophagic sequestration from the delivery of lysosomal enzymes | Journal of Cell...
To investigate the role of newly synthesized proteins during autophagic sequestration and degradation, the effects of protein synthesis inhibition on autophagic vacuole (AV) formation and degradation were analyzed. The inhibition of protein synthesis was found to separate autophagic sequestration from the delivery of lysosomal enzymes to (AVs). Pretreatment with cycloheximide for , or = 3 h caused a drastic inhibition of autophagy-induced degradation. Surprisingly, morphological analyses showed that the inhibition of protein synthesis for up to 12 h did not block the formation of nascent AVs; however, it did prevent their conversion into degradative AVs. Using immunoperoxidase cytochemistry with an antibody against cathepsin D and labeling of lysosomes with endocytosed colloidal gold, we found that the nascent AVs that formed during prolonged cycloheximide pretreatment had not received lysosomal markers. The inhibition of autophagic degradation and lysosomal enzyme delivery were rapidly reversed ...
Tumor Cell Autophagy as an Adaptive Response Mediating Resistance to Treatments Such as Antiangiogenic Therapy | Cancer ResearchTumor Cell Autophagy as an Adaptive Response Mediating Resistance to Treatments Such as Antiangiogenic Therapy | Cancer Research
Based on the preclinical evidence mentioned above, autophagy inhibition is currently being investigated as a means of modulating the response to cancer therapies in patients. Currently, the only U.S. Food and Drug Administration-approved agents that are able to inhibit autophagy are chloroquine, an antimalaria drug, and its derivative hydroxychloroquine, both of which block autophagy by disrupting lysosome acidification. One notable completed study was a randomized trial that combined chloroquine with conventional treatment, defined as radiation plus temozolomide, for glioblastoma. The median survival was 24 months with chloroquine treatment and 11 months without chloroquine treatment, a difference that was not quite statistically significant (40). The lack of statistical significance in that trial could mean that the effect is real but the sample size (30 patients total) was too small to achieve statistical significance, or it could mean that the observed difference was due to chance and there ...
Translating autophagy proteins: a novel aging pathway - The Kennedy Institute of RheumatologyTranslating autophagy proteins: a novel aging pathway - The Kennedy Institute of Rheumatology
With extension of the average lifespan, the ageing population has become a heavy burden for both society and individuals. Immune responses, key for the removal of pathogens and damage, are compromised in the elderly, making the elderly more susceptible to infections. In addition immune senescence is a risk factor for many late-onset diseases, such as cancer and atherosclerosis. Autophagy through degrading bulk cytoplasmic material maintains cytoplasmic health and cellular homeostasis [1]. We have found that it allows differentiation of immune cells [2] [3]. In previous work we showed that loss of autophagy in macrophages results in low-grade inflammation (inflamm-aging) and reduces innate and adaptive immune responses, typical of a senescent immune system. Autophagy induction rejuvenates immune responses in the elderly in T cells [3]. We have recently uncovered a novel pathway that controls the translation of autophagy proteins in T and B lymphocytes. Lymphocytes from old mice and elderly humans ...
Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain | Molecular Pain | Full TextSpinal autophagy is differently modulated in distinct mouse models of neuropathic pain | Molecular Pain | Full Text
Autophagy is a homeostatic degradative process essential for basal turnover of long-lived proteins and organelles as well as for removal of dysfunctional cellular components. Dysregulation of the autophagic machinery has been recently associated to several conditions including neurodegenerative diseases and cancer, but only very few studies have investigated its role in pain processing. We previously described autophagy impairment at the spinal cord in the experimental model of neuropathic pain induced by spinal nerve ligation (SNL). In this study, we characterized the main autophagic markers in two other common experimental models of neuropathic pain, the chronic constriction injury (CCI) and the spared nerve injury (SNI). The different modulation of LC3-I, Beclin 1 and p62 suggested that autophagy is differentially affected in the spinal dorsal horn depending on the type of peripheral injury. Confocal analysis of p62 distribution in the spinal dorsal horn indicated its presence mainly in NeuN-positive
Repositorio da Producao Cientifica e Intelectual da Unicamp: Defective regulation of adipose tissue autophagy in obesityRepositorio da Producao Cientifica e Intelectual da Unicamp: Defective regulation of adipose tissue autophagy in obesity
OBJECTIVES: Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. SUBJECTS: Adipose tissue autophagy was evaluated in mice and humans. RESULTS: First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was ...
Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation | The EMBO JournalInduction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation | The EMBO Journal
Our results demonstrate the importance of autophagy in SC activation. Autophagic flux appears to be too low to be detectable in QSCs, but increases along with ATP content occur during SC activation. Notably, the increased flux is detected at a time point when the majority of the cells have not yet entered the cell cycle. We show that inhibiting autophagy leads to a decrease in autophagic flux, a reduction in ATP content, and a delay in activation, suggesting a causal link between autophagic flux, bioenergetic status, and SC activation. That a partial rescue in the delay in activation can be achieved with sodium pyruvate confirms a bioenergetic requirement that autophagy may fulfill during activation. We also show that SIRT1, a known nutrient sensor, induces autophagic flux during SC activation and that its inhibition also causes a delay in SC activation.. Our findings parallel to those of Hubbard et al (2010) who demonstrated that autophagy produces energy required for another cellular process ...
Plus itPlus it
Autophagy is a catabolic process whereby damaged organelles and proteins are sequestered into autophagic vesicles, then degraded through fusion with lysosomes and reused as metabolic precursors. While autophagy can suppress tumorigenesis in normal tissues, stimulation of autophagy in established tumors promotes tumor cell survival under stressful metabolic and environmental conditions and can serve as a mechanism of treatment resistance. Yang and colleagues review the role of autophagy in cancer biology and discuss how autophagy can be exploited as a therapeutic target. While most cancer therapeutics induce autophagy, the functional consequence of autophagy induction in the context of cancer therapy continues to emerge.. ...
Ypt1 recruits the Atg1 kinase to the preautophagosomal structure | PNASYpt1 recruits the Atg1 kinase to the preautophagosomal structure | PNAS
The GTPase Ypt1 and its mammalian homolog Rab1 regulate three different trafficking events: autophagy, ER-Golgi, and intra-Golgi traffic (12). During autophagy, Ypt1 is recruited to the phagophore by the TRAPPIII complex, one of three multimeric Ypt1/Rab1 GEFs that localize to distinct cellular locations (12). These complexes share several essential subunits that are required for GEF activity. The TRAPPIII-specific subunit Trs85 specifically directs TRAPPIII to the phagophore where it recruits and activates Ypt1 on the autophagy pathway (14).. To determine where on the autophagy pathway TRAPPIII and Ypt1 act, we screened all known autophagy-deficient atg mutants for defects in the recruitment of Trs85 to the PAS. This screen revealed that the recruitment of TRAPPIII to the PAS is dependent on Atg17 and suggested that Ypt1 and its GEF act in the induction step of the pathway. Five Atg proteins act in induction: Atg1, Atg13, Atg17, Atg29, and Atg31 (6, 9). Of these, only Atg1 is recruited to the ...
Autophagy unveiled | JCBAutophagy unveiled | JCB
Thus the molecular description of autophagy is a relatively recent phenomenon (Klionsky and Emr, 2000). But the morphology came early. Autophagy is the destructive process in which a double membrane envelops cytoplasm and organelles before targeting them to lysosomes for destruction. It was first spotted in differentiating kidney cells as they redirected their metabolic energies (Clark, 1957).. A robust model was established by Ashford and Porter (1962), who spotted autophagy when glucagon was perfused into rat livers. Glucagon is made in response to low blood sugar levels, so autophagy may be the cells way of scaling back operations in hard times. In the words of Ashford and Porter (1962), the hydrolysis may be "providing the protoplast with breakdown products for use in a reoriented physiology," with the membrane "shield[ing] the rest of the cell from the general spread of the degradative process.". The word autophagy crept into the literature in the 1960s (Deter et al., 1967) as it became ...
Plus itPlus it
Autophagy, an essential homeostatic process by which cells degrade and recycle cytoplasmic components, has been implicated in both tumor suppression and tumorigenesis depending on the cancer type and context. The molecular determinants that dictate the effect of autophagy on tumor progression have not been defined. Rosenfeldt and colleagues identified the tumor suppressor p53 as a regulator of whether autophagy suppresses or promotes cancer in a Kras-driven mouse model of pancreatic ductal adenocarcinoma (PDAC). Pancreatic-specific expression of constitutively active Kras (KrasG12D) induces the formation of precancerous lesions that stochastically progress to PDAC. However, in KrasG12D mice also lacking the essential autophagy gene Atg7, precancerous lesions accumulated but never progressed to PDAC, suggesting a requirement for autophagy in tumor progression. These lesions exhibited elevated p53 levels, expression of senescence markers, and sustained growth arrest. Because p53 is inactivated in ...
Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice | Molecular...Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice | Molecular...
Current evidence suggests a central role for autophagy in many neurodegenerative diseases including Alzheimers disease, Huntingtons disease, Parkinsons disease and amyotrophic lateral sclerosis. Furthermore, it is well admitted that inflammation contributes to the progression of these diseases. Interestingly, crosstalks between autophagy and inflammation have been reported in vitro and at the peripheral level such as in Crohns disease. However, the impact of systemic inflammation on autophagic components in the brain remains to be documented. Therefore, this study monitored autophagy markers after acute and chronic lipopolysaccharide (LPS)-induced inflammatory stress in mice. We showed that acute inflammation, 24 h post-intraperitoneal 10 mg/kg LPS, substantially increased cytokine production (Interleukin(IL)-1β , Tumor necrosis factor (TNF)- α and IL-6), decreased the levels of autophagy markers (Beclin-1, p62 and LC3 II) and reduced p70S6K activation in cortex and hippocampus. In hippocampus, IL
Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells | Cell Death & DiseasePharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells | Cell Death & Disease
Sirtuin 6 (SIRT6) is a member of the NAD+-dependent class III deacetylase sirtuin family, which plays a key role in cancer by controlling transcription, genome stability, telomere integrity, DNA repair, and autophagy. Here we analyzed the molecular and biological effects of UBCS039, the first synthetic SIRT6 activator. Our data demonstrated that UBCS039 induced a time-dependent activation of autophagy in several human tumor cell lines, as evaluated by increased content of the lipidated form of LC3B by western blot and of autophagosomal puncta by microscopy analysis of GFP-LC3. UBCS039-mediated activation of autophagy was strictly dependent on SIRT6 deacetylating activity since the catalytic mutant H133Y failed to activate autophagy. At the molecular level, SIRT6-mediated autophagy was triggered by an increase of ROS levels, which, in turn, resulted in the activation of the AMPK-ULK1-mTOR signaling pathway. Interestingly, antioxidants were able to completely counteract UBCS039-induced autophagy,
Roles of autophagy in health and disease | Centro de Investigaciones Biológicas - CIBRoles of autophagy in health and disease | Centro de Investigaciones Biológicas - CIB
Our lab uses cellular and animal models to understand the roles of autophagy in both physiological and pathological conditions. Autophagy is an essential intracellular degradation pathway that recycles cell components, thereby generating new building blocks and energy to maintain cellular homeostasis. Autophagy plays an important part in the response to nutrient starvation and the recycling of damaged organelles, and serves as a key survival mechanism in conditions of stress.. We are interested in studying the relationships between autophagy and basic processes such as proliferation, differentiation, metabolism and cell death in order to gain further insight into the processes of development and physiological aging. Moreover, we seek to better understand the role of autophagy in a variety of pathologies, including cancer and neurodegenerative diseases, and to identify new treatments for human diseases by screening for drugs that target autophagy.. ...
Endoplasmic reticulum stress caused by aggregate-prone proteins containing homopolymeric amino acids. | PubFactsEndoplasmic reticulum stress caused by aggregate-prone proteins containing homopolymeric amino acids. | PubFacts
Many human proteins have homopolymeric amino acid (HPAA) tracts, but their physiological functions or cellular effects are not well understood. Previously, we expressed 20 HPAAs in mammalian cells and showed characteristic intracellular localization, in that hydrophobic HPAAs aggregated strongly and caused high cytotoxicity in proportion to their hydrophobicity. In the present study, we investigated the cytotoxicity of these aggregate-prone hydrophobic HPAAs, assuming that the ubiquitin proteasome system is impaired in the same manner as other well-known aggregate-prone polyglutamine-containing proteins. Some highly hydrophobic HPAAs caused a deficiency in the ubiquitin proteasome system and excess endoplasmic reticulum stress, leading to apoptosis. These results indicate that the property of causing excess endoplasmic reticulum stress by proteasome impairment may contribute to the strong cytotoxicity of highly hydrophobic HPAAs, and proteasome impairment and the resulting excess endoplasmic ...
SciCombinator - Upregulation of autophagy-related gene 5 protects dopaminergic neurons in a zebrafish model of Parkinsons...SciCombinator - Upregulation of autophagy-related gene 5 protects dopaminergic neurons in a zebrafish model of Parkinson's...
Comments, concepts and statistics about Upregulation of autophagy-related gene 5 protects dopaminergic neurons in a zebrafish model of Parkinsons disease.
Autophagy-related protein elisa and antibodyAutophagy-related protein elisa and antibody
Shop Autophagy-related protein ELISA Kit, Recombinant Protein and Autophagy-related protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Autophagy-related protein 13 - WikipediaAutophagy-related protein 13 - Wikipedia
Autophagy-related protein 13 also known as ATG13 is a protein that in humans is encoded by the KIAA0652 gene. ATG13 is an autophagy factor required for phagosome formation. ATG13 is a target of the TOR kinase signaling pathway that regulates autophagy through phosphorylation of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. GRCh38: Ensembl release 89: ENSG00000175224 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000027244 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: KIAA0652". Mercer CA, Kaliappan A, Dennis PB (July 2009). "A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy". Autophagy. 5 (5): 649-62. doi:10.4161/auto.5.5.8249. PMID 19287211. Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, Guan JL, Oshiro N, Mizushima N (April 2009). "Nutrient-dependent mTORC1 Association with the ULK1-Atg13-FIP200 Complex Required ...
Tri-dimensional exploration of membrane assembly during autophagosome biogenesisTri-dimensional exploration of membrane assembly during autophagosome biogenesis
The goal of this project is to unveil how membranes are assembled into autophagosomes. We will uniquely combine yeast Saccharomyces cerevisiae genetics and immuno-electron tomography to reach this objective. At first, we will devise a novel electron tomography protocol to preserve yeast autophagosomal membranes near their native state and be able immunolabel them. Subsequently, we will exploit this procedure to develop a model about how autophagosomal membranes are assembled into autophagosomes by analysing the precursor structures accumulated in yeast autophagy mutants. This unique experimental system will allow us visualizing the formation of autophagosomes through 3-dimentional images with ultrastructural resolution, and determine the distribution of Atg proteins, thus acquitting insights into their function ...
Aging | MeCP2 inhibits cell functionality through FoxO3a and autophagy in endothelial progenitor cells - FigureAging | MeCP2 inhibits cell functionality through FoxO3a and autophagy in endothelial progenitor cells - Figure
Objectives: Autophagy is an evolutionarily conserved intracellular degradation mechanism in which cell constituents are phagocytosed to maintain cellular homeostasis. Forkhead box O 3a (FoxO3a) promotes autophagy to protect cells from environmental stress. Methylated CpG binding protein 2 (MeCP2) is a nuclear protein that binds DNA and represses transcription. However, the mechanism and interplay between FoxO3a and MeCP2 underlying endothelial progenitor cell (EPC) function are not fully understood.Results: In EPCs, MeCP2 overexpression attenuated autophagy and cell functionality, which were reversed by the autophagy activator rapamycin or co-transfection with FoxO3a. FoxO3a promoted cell function, which was reversed by the autophagy inhibitor chloroquine. Following MeCP2 overexpression, MeCP2 was found enriched on the FoxO3a promoter, resulting in promoter hypermethylation and enhanced H3K9 histone modification in nucleosomes of the FoxO3a promoter.Conclusions: MeCP2 attenuated cell functionality via
Tumor cells evade death through autophagy ( Autophagy is a cellular process that en...)Tumor cells evade death through autophagy ( Autophagy is a cellular process that en...)
Autophagy is a cellular process that enables cells to turnover their c...In the study which appears online on January 18 in advance of publica...,Tumor,cells,evade,death,through,autophagy,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
Plus itPlus it
Purpose: Triple-negative breast cancers (TNBC) are defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (ERBB2/HER2). Although initially responsive to chemotherapy, most recurrent TNBCs develop resistance, resulting in disease progression. Autophagy is a lysosome-mediated degradation and recycling process that can function as an adaptive survival response during chemotherapy and contribute to chemoresistance. Our goal was to determine whether autophagy inhibition improves treatment efficacy in TNBC cells in tumors either sensitive or refractory to anthracyclines.. Experimental Design: We used in vitro and in vivo models of TNBC using cell lines sensitive to epirubicin and other anthracyclines, as well as derivative lines, resistant to the same drugs. We assessed basal autophagy levels and the effects of chemotherapy on autophagy in parental and resistant cells. Applying various approaches to inhibit autophagy alone ...
Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans | Nature CommunicationsHormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans | Nature Communications
Stress-response pathways have evolved to maintain cellular homeostasis and to ensure the survival of organisms under changing environmental conditions. Whereas severe stress is detrimental, mild stress can be beneficial for health and survival, known as hormesis. Although the universally conserved heat-shock response regulated by transcription factor HSF-1 has been implicated as an effector mechanism, the role and possible interplay with other cellular processes, such as autophagy, remains poorly understood. Here we show that autophagy is induced in multiple tissues of Caenorhabditis elegans following hormetic heat stress or HSF-1 overexpression. Autophagy-related genes are required for the thermoresistance and longevity of animals exposed to hormetic heat shock or HSF-1 overexpression. Hormetic heat shock also reduces the progressive accumulation of PolyQ aggregates in an autophagy-dependent manner. These findings demonstrate that autophagy contributes to stress resistance and hormesis, and reveal a
The structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy | The EMBO JournalThe structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy | The EMBO Journal
Autophagy is the process through which the bulk degradation of cytoplasmic components by the lysosomal/vacuolar system occurs (Klionsky and Ohsumi, 1999), and it has a critical function in numerous biological processes (Mizushima, 2007). In autophagy, a double‐membrane structure called an autophagosome sequesters a portion of the cytoplasm and fuses with the lysosome/vacuole to deliver its contents into the organelle lumen (Baba et al, 1994). Genetic approaches in Saccharomyces cerevisiae have identified many autophagy‐related (ATG) genes involved in this process (Klionsky et al, 2003), and subsequent biochemical analyses have demonstrated that a novel ubiquitin‐like conjugation system called the Atg8 system is essential for autophagosome formation (Ichimura et al, 2000). In the Atg8 system, nascent Atg8 is cleaved at its C‐terminal arginine residue by Atg4, a cysteine protease (Kirisako et al, 2000), and the exposed C‐terminal glycine is conjugated to phosphatidylethanolamine (PE) by ...
mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntingtons disease |...mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington's disease |...
Huntingtons disease (HD) is a neurodegenerative disease caused by an expansion in the huntingtin protein (also called Htt) that induces neuronal cell death with age. We found that the treatment of 12-month-old symptomatic heterozygous and homozygous zQ175 huntingtin knockin mice for 12 weeks with CTEP, a negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), reduced the size and number of huntingtin aggregates, attenuated caspase-3 activity, and reduced both neuronal apoptosis and neuronal loss in brain tissue. Both motor and cognitive impairments were improved in CTEP-treated zQ175 mice. The reduction in huntingtin protein aggregate burden by CTEP correlated with the activation of an autophagy pathway mediated by the kinase GSK3β, the transcription factor ZBTB16, and the autophagy factor ATG14. Inhibition of mGluR5 with CTEP also reduced the inhibitory phosphorylation of the autophagosome biogenesis-related kinase ULK1, increased the phosphorylation of the autophagy ...
U-M researcher examines the cell s housekeeping habitsU-M researcher examines the cell s housekeeping habits
Autophagy may even provide a clue to the mythical fountain of youth. Autophagy activity is known to decrease with aging, and experiments in which autophagy was blocked in the C. elegans nematode worm resulted in dramatically shorter life spans for the 1 millimeter creatures. Conversely, more autophagy may prolong life. This fits with findings that caloric restriction can extend the life span in rats, since near-starvation triggers more autophagy as the cells recycle parts of themselves for fuel. Sustained autophagy may also increase longevity by protecting cells against free radical damage and mutations in DNA. "This is becoming a very hot field," Klionsky said. "We have a lot of really interesting questions to explore in autophagy ...
Atg2A · QED Bioscience IncAtg2A · QED Bioscience Inc
Autophagy is a catabolic process that results in the degradation of bulk cytoplasmic contents within autophagosomes and lysosomes. Two human Atg2 homologs (Atg2A, Atg2B) are critical for autophagosome formation as silencing of both results in the accumulation of unclosed autophagic structures. Starvation-induced autophagy targets Atg2A to the initiation site of autophagosome biogenesis, where it associates with DFCP1, WIPI-1, and other autophagy- related proteins. Atg2 proteins also function in lipid droplet metabolism as depletion of both Atg2A and AtgB results in changes in the size, number, and distribution of lipid droplets. An increase in Atg2A expression during etoposide- and doxorubicin-induced apoptosis suggests that Atg2A may be a useful indicator of topoisomerase II inhibitor-mediated apoptosis.. ...
Involvement of autophagy in ovarian cancer: a working hypothesis | Journal of Ovarian Research | Full TextInvolvement of autophagy in ovarian cancer: a working hypothesis | Journal of Ovarian Research | Full Text
As compared to benign hyperplastic tissues and borderline ovarian tumors, poorly differentiated and highly malignant ovarian cancer cells were shown to express very low level of the autophagy protein LC3 [58], indicating that LC3-labeled autophagosomes do not accumulate in highly aggressive ovarian cancers. Whether this phenomenon underlies the inability to form autophagosomes or rather reflects their efficient removal by the lysosomal system remains to be elucidated. Mutation and deletion of the oncosuppressor P53 gene has been reported in 60-80% of both sporadic and familial ovarian cancers [56]. DNA-binding deficient p53 mutants are unable to sequester bcl-2 or bcl-XL, and display a dominant negative activity. Bcl-2 can inhibit the formation of the autophagy interactome by interacting with beclin 1 [20], and therefore the over-expression of such mutated p53 in ovarian cancer cells may indirectly impact on autophagy. In addition, p53 mutants that permanently localizes in the cytoplasm have ...
JCI - Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma...JCI - Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma...
Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3-dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an ...
JCI - Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma...JCI - Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma...
Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3-dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an ...
Go to Differential role of autophagy in CD4 T cells and macrophages during X4 and R5 HIV-1 infection.Go to Differential role of autophagy in CD4 T cells and macrophages during X4 and R5 HIV-1 infection.
BACKGROUND: HIV-1 can infect and replicate in both CD4 T cells and macrophages. In these cell types, HIV-1 entry is mediated by the binding of envelope glycoproteins (gp120 and gp41, Env) to the receptor CD4 and a coreceptor, principally CCR5 or CXCR4, depending on the viral strain (R5 or X4, respectively). Uninfected CD4 T cells undergo X4 Env-mediated autophagy, leading to their apoptosis, a mechanism now recognized as central to immunodeficiency. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate here that autophagy and cell death are also induced in the uninfected CD4 T cells by HIV-1 R5 Env, while autophagy is inhibited in productively X4 or R5-infected CD4 T cells. In contrast, uninfected macrophages, a preserved cell population during HIV-1 infection, do not undergo X4 or R5 Env-mediated autophagy. Autophagosomes, however, are present in macrophages exposed to infectious HIV-1 particles, independently of coreceptor use. Interestingly, we observed two populations of autophagic cells: one ...
Plus itPlus it
Purpose: Understanding the roles of mammalian autophagy in cancer highlights recent advances in the pharmacologic manipulation of autophagic pathways as a therapeutic strategy for cancer. However, autophagy status and corresponding functions in hepatocellular carcinoma (HCC) after therapeutic stress remain to be clarified. This study was to determine whether the autophagic machinery could be activated after chemotherapy and the contribution of autophagy to tolerance of oxaliplatin in HCC.. Experimental Design: Autophagy activation and cell death induced by oxaliplatin were examined in two HCC cell lines as well as in vivo using an HCC model in nude mice. HCC tissue samples with or without locoregional chemotherapy before surgery were also examined by immunohistochemical and electron microscopic analysis.. Results: Autophagy was functionally activated in HCC cell lines and xenografts after oxaliplatin treatment. Suppression of autophagy using either pharmacologic inhibitors or RNA interference of ...
Autophagy as a Regulated Pathway of Cellular Degradation | ScienceAutophagy as a Regulated Pathway of Cellular Degradation | Science
Biosynthetic transport and organelle turnover. Autophagy is a ubiquitous process that occurs in plant, animal, and fungal cells. Although autophagy is generally considered to be nonselective, the protein components required for autophagic uptake are also used in specific transport events. For example, as noted above, autophagy in yeast overlaps with the biosynthetic Cvt pathway that transports aminopeptidase I (API) to the vacuole. API is synthesized as a precursor in the cytosol and rapidly oligomerizes into a dodecamer (46). The dodecameric precursor API assembles into a larger complex composed of multiple dodecamers, termed a Cvt complex. The Cvt complex is then enwrapped by a double-membrane that forms a cytosolic vesicle. This Cvt vesicle is smaller than an autophagosome and appears to exclude cytosol (12, 13). After fusion with the vacuole, the inner vesicle is degraded in the lumen, allowing release and maturation of precursor API.. In addition to the biosynthetic transport of precursor ...
研究内容｜School of medicine, Niigata University研究内容｜School of medicine, Niigata University
Figure 2) Physiological and pathological relevance of selective types of autophagy. (a) Autophagy operates constitutively at low levels, even under nutrient-rich conditions, and mediates the global turnover of cytoplasmic material. Defects in autophagy are accompanied by the disruption of tissue homeostasis, resulting in life-threatening diseases.(b) The LC3-binding proteins p62 and Nbr1 have a UBA domain through which they can mediate the sequestration of ubiquitinated cargos into autophagosomes. Meanwhile, p62 itself is also a specific substrate for autophagy. Defective autophagy is usually accompanied by the extensive accumulation of p62, which enhances its function as a scaffold protein in several signaling pathways, e.g., NF-κB signaling, apoptosis, and Nrf2 activation. Such abnormalities might be involved in tumorigenesis and Paget disease of bone. (c) Nix/Bnip3 localizes to mitochondria and leads to their depolarization, which is indispensable for mitophagy during erythroid ...
Expression of JAK Proteins and Autophagy Markers in Sjögrens Syndrome Patients - ACR Meeting AbstractsExpression of JAK Proteins and Autophagy Markers in Sjögren's Syndrome Patients - ACR Meeting Abstracts
Background/Purpose: Sjögrens syndrome (SS) is an autoimmune epitheliitis that mainly affects the salivary and lachrymal glands. The glandular hypofunction has been associated to loss of epithelium by apoptosis. However, several lines of evidence indicate the existence of survival mechanisms that counteract the apoptosis, one of them being the autophagy. This mechanism is involved in decreasing inflammation by selectively removing proteins related to Toll-like receptors and inflammasomes, among other pathways. A previous study on SS showed increased autophagy in T lymphocytes of salivary glands, but the glandular epithelium was not evaluated. Interestingly, IL-6 implicated in SS pathogenesis mediates its response activating the JAK-STAT signaling pathway. In macrophages and other cellular types, activation of the JAK-STAT pathway inhibits autophagy. Studies in SS have shown increased expression of STATs, however, expression of JAK proteins has not been evaluated. The aim of this study was to ...
Serval - Autophagy induction does not protect retina against apoptosis in ischemia/reperfusion model.Serval - Autophagy induction does not protect retina against apoptosis in ischemia/reperfusion model.
The role played by autophagy after ischemia/reperfusion (I/R) in the retina remains unknown. Our study investigated whether ischemic injury in the retina, which causes an energy crisis, would induce autophagy. Retinal ischemia was induced by elevation of the intraocular pressure and modulation of autophagic markers was analyzed at the protein levels in an early and late phase of recovery. Following retinal ischemia an increase in LC3BII was first observed in the early phase of recovery but did not stay until the late phase of recovery. Post-ischemic induction of autophagy by intravitreal rapamycin administration did not provide protection against the lesion induced by the ischemic stress. On the contrary, an increase in the number of apoptotic cells was observed following I/R in the rapamycin treated retinas.
Palmitate Activates Autophagy in INS-1E β-Cells and in Isolated Rat and Human Pancreatic IsletsPalmitate Activates Autophagy in INS-1E β-Cells and in Isolated Rat and Human Pancreatic Islets
We have investigated the in vitro effects of increased levels of glucose and free fatty acids on autophagy activation in pancreatic beta cells. INS-1E cells and isolated rat and human pancreatic islets were incubated for various times (from 2 to 24 h) at different concentrations of glucose and/or palmitic acid. Then, cell survival was evaluated and autophagy activation was explored by using various biochemical and morphological techniques. In INS-1E cells as well as in rat and human islets, 0.5 and 1.0 mM palmitate markedly increased autophagic vacuole formation, whereas high glucose was ineffective alone and caused little additional change when combined with palmitate. Furthermore, LC3-II immunofluorescence co-localized with that of cathepsin D, a lysosomal marker, showing that the autophagic flux was not hampered in PA-treated cells. These effects were maintained up to 18-24 h incubation and were associated with a significant decline of cell survival correlated with both palmitate concentration and
Pesquisa | Portal Regional da BVSPesquisa | Portal Regional da BVS
Macroautophagy (autophagy) is an evolutionarily conserved recycling and stress response mechanism. Active at basal levels in eukaryotes, autophagy is upregulated under stress providing cells with building blocks such as amino acids. A lysosome-integrated sensor system composed of RRAG GTPases and MTOR complex 1 (MTORC1) regulates lysosome biogenesis and autophagy in response to amino acid availability. Stress-mediated inhibition of MTORC1 results in the dephosphorylation and nuclear translocation of the TFE/MITF family of transcriptional factors, and triggers an autophagy- and lysosomal-related gene transcription program. The role of family members TFEB and TFE3 have been studied in detail, but the importance of MITF proteins in autophagy regulation is not clear so far. Here we introduce for the first time a specific role for MITF in autophagy control that involves upregulation of MIR211. We show that, under stress conditions including starvation and MTOR inhibition, a MITF-MIR211 axis ...
Plus itPlus it
It is generally thought that when chemotherapy and radiation promote autophagy in tumor cells, the autophagy has a cytoprotective function that can be inhibited to sensitize the cells to treatment. We and our collaborators recently demonstrated lack of sensitization to radiation as well as to cisplatin in the 4T1 murine breast cancer model upon autophagy inhibition, indicating the existence of a nonprotective function of autophagy in tumor cells (Maycotte et al., 2012; Bristol et al., 2013).. In this work, we demonstrate a lack of sensitization to radiation in Hs578t breast cancer cells upon inhibition of radiation-induced autophagy utilizing both multiple pharmacological approaches as well as confirming these results with genetic silencing of Beclin-1. The concept that inhibition of autophagy fails to sensitize Hs578t cells to radiation therapy is supported by the lack of increased apoptosis when autophagy is inhibited, which supports the absence of cytoprotective autophagy. At the same time, ...
Autophagy - The School of Biomedical Sciences WikiAutophagy - The School of Biomedical Sciences Wiki
Autophagy is an essential cellular process, used by cells to degrade damaged and unnecessary cytosolic macromolecules and organelles, for example, proteins[1]. This prevents cell functions and pathways from being damaged or interrupted by aggregates of proteins or non-functioning organelles, a key cause of disease. Diseases associated with abnormal autophagy include Parkinsons Disease, osteoarthritis and cancer[2][3]. Autophagy proceeds via a five-step mechanism that starts with the sequestration of cytosolic material by a double-membrane, known as a phagophore. Once the phagophore membrane ends fuse to form a vesicle, the substrate has been fully sequestered. Once sequestration is complete, the autophagosome fuses with a lysosome and up to 40 hydrolytic enzymes digest the autophagosomes cargo[4]. Autophagy helps the cell maintain a stable internal environment and prevents damage occurring to the cell/ tissues by removing harmful molecules and preventing their accumulation[5]. It is ...
Addiction to Life-Saving, Self-Digestion Process Can Aid Cancer Cells in Tumor Growth - Healthcanal.com : Healthcanal.comAddiction to Life-Saving, Self-Digestion Process Can Aid Cancer Cells in Tumor Growth - Healthcanal.com : Healthcanal.com
They also showed that the inhibition of that process could prove to be a valuable treatment approach for aggressive cancers. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.. Autophagy is a cellular self-cannibalization process where cells eat themselves to survive starvation. Eileen White, PhD, associate director for basic science at CINJ, and collaborators previously discovered that cancer cells can take advantage of the autophagy survival pathway to aid their growth into tumors. In this new study, Dr. White and colleagues have found that cancer cells induce autophagy and this self-cannibalization process enables the growth of the most aggressive tumors.. The latest research, which appears online and in the March print editions of Genes & Development, focuses on cancer genes known as H-ras and K-ras that are activated in many aggressive cancers with poor prognoses. These cancers, which are acutely sensitive to autophagy inhibition, have high levels of autophagy that ...
Aberrant Aur-A signaling is certainly linked with tumor cancerous manners. metabolic - Small Molecule Inhibitors of Protein...Aberrant Aur-A signaling is certainly linked with tumor cancerous manners. metabolic - Small Molecule Inhibitors of Protein...
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 ...
Autophagy - The School of Biomedical Sciences WikiAutophagy - The School of Biomedical Sciences Wiki
Macroautophagy - This is widely considered to be the most used pathway of autophagy in the body. It deals with the recycling of dysfunctional organelles and proteins which may have been damaged or incorrectly folded during their synthesis. The process starts with a piece of cellular machinery termed the isolation membrane or "phagophore". This is a double membrane structure that elongates and encloses part of the cytoplasm, as well as the target organelles or proteins. The resulting specialised vesicle is termed an "autophagosome". The autophagosome then migrates to a lysosome to which it fuses via the outer membrane. It is important to note the outer membrane stays intact thus keeping the contents and Hydrolases within the "autolysosome" for recycling[8][9]. Microautophagy - This process differs from macroautophagy as it is only concerned with the degradation and recycling of cytoplasm in the cell. It also uses a different mechanism. No autophagosome is formed as the lysosome itself directly ...
Valosin-containing protein is a key mediator between autophagic cell death and apoptosis in adult hippocampal neural stem cells...Valosin-containing protein is a key mediator between autophagic cell death and apoptosis in adult hippocampal neural stem cells...
Programmed cell death (PCD) is a deliberate cellular suicide process. Dysfunction of PCD is implicated in various human diseases, including developmental and neurodegenerative disorders, cancer and autoimmune diseases [1]. PCD can be categorized by morphological criteria [2]. Type I cell death, known as apoptosis, is characterized by cell shrinkage, nuclear condensation, membrane blebbing, mitochondria dysfunction, loss of selectivity in membrane permeabilization, and nuclear DNA fragmentation. Lastly, cells are rapidly eliminated by phagocytosis [3]. Type II PCD refers to autophagic cell death (ACD). Autophagy is a catabolic process that disposes of various cytoplasmic components, including protein aggregates and organelles [4]. The components are sequestered by autophagosomes, which fuse with lysosomes for degradation. This process usually occurs in response to cellular stress to protect the cells. However, prolonged autophagy can cause ACD [5]. Type III cell death, called necrosis, is best ...
The bifunctional autophagic flux by 2-deoxyglucose to control survival or growth of prostate cancer cells | BMC Cancer | Full...The bifunctional autophagic flux by 2-deoxyglucose to control survival or growth of prostate cancer cells | BMC Cancer | Full...
Recent reports using metabolism regulating drugs showed that nutrient deprivation was an efficient tool to suppress cancer progression. In addition, autophagy control is emerging to prevent cancer cell survival. Autophagy breaks down the unnecessary cytoplasmic components into anabolic units and energy sources, which are the most important sources for making the ATP that maintains homeostasis in cancer cell growth and survival. Therefore, the glucose analog 2-deoxyglucose (2DG) has been used as an anticancer reagent due to its inhibition of glycolysis. Prostate cancer cells (PC3) were treated with 2DG for 6 h or 48 h to analyze the changing of cell cycle and autophagic flux. Rapamycin and LC3B overexpressing vectors were administered to PC3 cells for autophagy induction and chloroquine and shBeclin1 plasmid were used to inhibit autophagy in PC3 cells to analyze PC3 cells growth and survival. The samples for western blotting were prepared in each culture condition to confirm the expression level of
ALZFORUM | NETWORKING FOR A CUREALZFORUM | NETWORKING FOR A CURE
The extreme scarcity of autophagic vacuoles in normal brain and their appearance in states of disease have previously led many to assume that autophagy in neurons is mainly an inducible process. Autophagy is solely responsible for organelle turnover, however, and the large cytoplasmic mass of neurons would suggest, therefore, that autophagy might have a significant constitutive component. The two papers by Komatsu et al. and Hara et al. have now provided elegant and definitive evidence in neurons for constitutive autophagy and have demonstrated that it is required for neuron survival. In fact, the results imply that the brain may actually be one of the tissues most vulnerable to a possible impairment of autophagy. These findings, therefore, offer insight into why neurons are preferentially victimized in diseases that disrupt the lysosomal system, even when the disease is a systemic one.. This new evidence for actively ongoing autophagy in neurons, which normally proceeds in the absence of ...
Crohn DiseaseCrohn Disease
To investigate the role of autophagy in T cells in vivo, two mouse genetic model systems have been employed. Since mice lacking the essential autophagy genes Atg5 or Atg7 die within the first 24-48 h of birth (Komatsu et al. 2005 Kuma et al. 2004), the role of autophagy in T cells has been studied using Atg5 fetal liver chimeric mice as well as Atg7f f Lck-Cre mice with a conditional deletion early in thymocyte development (Pua et al. 2007 Pua et al. 2009). In both mice, there are subtle but.... ...
Liver oxidative stress, apoptosis, and autophagy are increased in a mouse model of iron overloadLiver oxidative stress, apoptosis, and autophagy are increased in a mouse model of iron overload
Chua, A. and Domenichini, A. and Delima, R. and Elsegood, C. and Olynyk, J. and Trinder, D. 2017. Liver oxidative stress, apoptosis, and autophagy are increased in a mouse model of iron overload, pp. 4-4 ...
KEGG PATHWAY: Autophagy - animal - Homo sapiens (human)KEGG PATHWAY: Autophagy - animal - Homo sapiens (human)
Autophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily conserved among eukaryotes and exquisitely regulated. This progress initiates with production of the autophagosome, a double-membrane intracellular structure of reticular origin that engulfs cytoplasmic contents and ultimately fuses with lysosomes for cargo degradation. Autophagy is regulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation and ER stress. Constitutive level of autophagy plays an important role in cellular homeostasis and maintains quality control of essential cellular components ...
Tat-beclin 1 | Autophagy Activator | MedChemExpressTat-beclin 1 | Autophagy Activator | MedChemExpress
Tat-beclin 1, a peptide derived from a region of the autophagy protein (beclin 1), is a potent inducer of autophagy and interacts with negative regulator of autophagy, GAPR-1 (GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya (CHIKV) or West Nile virus (WNV). - Mechanism of Action & Protocol.
Influence of autophagy on the efficacy of radiotherapy | Radiation Oncology | Full TextInfluence of autophagy on the efficacy of radiotherapy | Radiation Oncology | Full Text
Autophagy plays an important role in cancer because of its tumour suppressing and tumour protecting function. For tumour suppressing function at the initiation stage, ATG Beclin-1 (Fig. 1) was identified as a tumour suppressor gene as it is mono-allelically deleted in many cases including ovarian cancers (75%), breast cancers (50-70%) and prostate cancers (40%) [5]. Also, Beclin-1 is allelically deleted and weakly expressed in most human breast carcinoma cell lines while the normal epithelium cells demonstrated a much higher expression [6]. In addition, overexpression of Beclin-1 in human breast carcinoma cell line MCF-7 cells could reduce tumourigenesis by inhibiting cell proliferation in a xenograft model [2]. Thus, low expression of Beclin-1 could favour the development of cancer. For colorectal and gastric cancers, associations were found with the down-regulation of Bif-1 and Atg2B, Atg5, Atg9B and Atg12 mutations, which led to inhibition of programmed cell death in colon cancer (Fig. 1). ...
Autophagy: Cancer, Other Pathologies, Inflammation, by M. A. Hayat - WORKPLACESAFETYEXPERTS.COM E-booksAutophagy: Cancer, Other Pathologies, Inflammation, by M. A. Hayat - WORKPLACESAFETYEXPERTS.COM E-books
It occurs at low basal levels under normal conditions, and is important for the turnover of organelles. Autophagy is upregulated in the heart in response to stress such as ischemia/reperfusion. Studies of ischemia/ reperfusion injury indicate that ROS and mitochondria are critical targets of injury, as opening of the mitochondrial permeability transition pore culminates in cell death. However, Sciarretta et al. (2011) indicate that autophagy is beneficial during ischemia but harmful during reperfusion. 2011). The receptor-mTOR complex positively regulates cell growth, and its inhibition causes a significant decrease in AUTOPHAGY 14 1. INTRODUCTION TO AUTOPHAGY cell size. The raptor part of the mTOR pathway modulates a large number of major processes that are listed here. Rapamycin binds to the FKBP12 protein, forming a drug-receptor complex which then interacts with and perturbs TOR. TOR is the central component of a complex signaling network that regulates cell growth and proliferation. The ...
Frontiers | DNA Damage Response and Autophagy: A Meaningful Partnership | GeneticsFrontiers | DNA Damage Response and Autophagy: A Meaningful Partnership | Genetics
Autophagy and the DNA damage response (DDR) are biological processes essential for cellular and organismal homeostasis. Herein we summarize and discuss emerging evidence linking DDR to autophagy. We highlight published data suggesting that autophagy is activated by DNA damage and is required for several functional outcomes of DDR signaling, including repair of DNA lesions, senescence, cell death, and cytokine secretion. Uncovering the mechanisms by which autophagy and DDR are intertwined provides novel insight into the pathobiology of conditions associated with accumulation of DNA damage, including cancer and aging, and novel concepts for the development of improved therapeutic strategies against these pathologies.
Autophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural studyAutophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural study
Peripheral neuropathy includes a wide range of diseases affecting millions around the world, and many of these diseases have unknown etiology. Peripheral neuropathy in diabetes represents a large proportion of peripheral neuropathies. Nerve damage can also be caused by trauma. Peripheral neuropathies are a significant clinical problem and efficient treatments are largely lacking. In the case of a transected nerve, different methods have been used to repair or reconstruct the nerve, including the use of nerve conduits, but functional recovery is usually poor.. Autophagy, a cellular mechanism that recycles damaged proteins, is impaired in the brain in many neurodegenerative diseases affecting animals and humans. No research, however, has investigated the presence of autophagy in the human peripheral nervous system. In this study, I present the first structural evidence of autophagy in human peripheral nerves. I also show that the density of autophagy structures is higher in peripheral nerves of ...
Measuring autophagy: a study of tools and methods for application and suitability in any cell type | NIH Research FestivalMeasuring autophagy: a study of tools and methods for application and suitability in any cell type | NIH Research Festival
Autophagy is a process by which cells can regulate their metabolism in times of starvation. It is also used to recycle damaged proteins and other cellular macromolecules. A growing number of human illnesses, including cancers and neurodegenerative diseases, have autophagy misregulation as either a component or a cause. We were therefore interested in assessing methods of analyzing autophagy in any cell, including in primary patient samples. Multiple publicly available dyes have been tested for ability to selectively stain autophagosomes, as marked by LC3, or lysosomes, as marked by LAMP-1. Additionally, a tandem-tagged LC3-GFP-RFP reporter construct was assessed. The tandem tag takes advantage of GFP degradation in the lysosome. Early autophagosomes, the LC3-GFP-RFP protein fluoresces both green and red, whereas the GFP signal is degraded in later autophagosomes as the pH decreases, so the vesicles become red-fluorescent only. This construct can therefore be used to track autophagic flux. ...
Plus itPlus it
CD47-specific antibodies and fusion proteins that block CD47-SIRPα signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in non-small cell lung cancer (NSCLC). SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux, including formation and accumulation of autophagosomes, fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes. Meanwhile, reactive oxygen species and inactivation of mTOR were shown to be involved in autophagy initiation in SIRPαD1-Fc-treated cells, indicating a probable mechanism for autophagy activation after targeting CD47 by SIRPαD1-Fc. Inhibition of autophagy enhanced macrophage-mediated phagocytosis ...
Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic...Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic...
Multiple lines of evidence support the idea that autophagy plays an essential role in the development of drug resistance, self-renewal, differentiation, and tumorigenic potentials of cancer stem cells (CSCs). Rottlerin (ROT) is widely used as a protein kinase C-delta (PKC-δ) inhibitor. Recent studies revealed that ROT induces apoptosis through engagement of mitochondria. However, it is not known whether ROT-induced apoptosis is associated with other mechanisms such as autophagy. Here we found that ROT induced autophagy followed by induction of apoptosis via inhibition of PI3K/Akt/mTOR pathway and activation of caspase cascade in human pancreatic CSCs. ROT induced a dose- and time-dependent inhibition of cell survival and induction of cytoplasmic vacuolations. The conversion of microtubule-associated protein LC3-I to LC3-II, and increased accumulations of Atg7 and Beclin-1 were also observed in CSCs treated with ROT. Prolonged exposure of CSCs to ROT eventually caused apoptosis which was ...
Modulation of intracellular calcium homeostasis blocks autophagosome formation. - Nuffield Department of Surgical SciencesModulation of intracellular calcium homeostasis blocks autophagosome formation. - Nuffield Department of Surgical Sciences
Cellular stress responses often involve elevation of cytosolic calcium levels, and this has been suggested to stimulate autophagy. Here, however, we demonstrated that agents that alter intracellular calcium ion homeostasis and induce ER stress-the calcium ionophore A23187 and the sarco/endoplasmic reticulum Ca (2+)-ATPase inhibitor thapsigargin (TG)-potently inhibit autophagy. This anti-autophagic effect occurred under both nutrient-rich and amino acid starvation conditions, and was reflected by a strong reduction in autophagic degradation of long-lived proteins. Furthermore, we found that the calcium-modulating agents inhibited autophagosome biogenesis at a step after the acquisition of WIPI1, but prior to the closure of the autophagosome. The latter was evident from the virtually complete inability of A23187- or TG-treated cells to sequester cytosolic lactate dehydrogenase. Moreover, we observed a decrease in both the number and size of starvation-induced EGFP-LC3 puncta as well as reduced numbers of
Disruption of the ribosomal P complex leads to stress-induced autophagy. | Sigma-AldrichDisruption of the ribosomal P complex leads to stress-induced autophagy. | Sigma-Aldrich
Sigma-Aldrich offers abstracts and full-text articles by [Ana Artero-Castro, Mileidys Perez-Alea, Andrea Feliciano, Jose A Leal, Mónica Genestar, Josep Castellvi, Vicente Peg, Santiago Ramón Y Cajal, Matilde E L Lleonart].
Defective autophagy in melanoma development and progression: role of oncogenic B-RAF signalling - ePrints - Newcastle UniversityDefective autophagy in melanoma development and progression: role of oncogenic B-RAF signalling - ePrints - Newcastle University
Full text for this publication is not currently held within this repository. Alternative links are provided below where available. ...
How Autophagy Helps the Body Cleanse Itself | Wellness MamaHow Autophagy Helps the Body Cleanse Itself | Wellness Mama
Self-eating or autophagy may sound alarming but is a natural cleansing process for the body. Learn how to help it along with fasting, sauna, and exercise.
Ambra1 - Activating molecule in BECN1-regulated autophagy protein 1 - Mus musculus (Mouse) - Ambra1 gene & proteinAmbra1 - Activating molecule in BECN1-regulated autophagy protein 1 - Mus musculus (Mouse) - Ambra1 gene & protein
Regulates autophagy and development of the nervous system. Involved in autophagy in controlling protein turnover during neuronal development, and in regulating normal cell survival and proliferation.
Achievements - Institute of Basic Medical SciencesAchievements - Institute of Basic Medical Sciences
We have shown that autophagic degradation regulates both the basal turnover and the therapy-induced elimination of the aggregate-prone oncoprotein PML/RARA, associated with acute promyelocytic leukemia (APL). This study also revealed an important role of autophagy in promoting granulocytic differentiation of APL cells (Isakson et al, Blood 2010). However, this does not seem to be a general feature of leukemic fusion oncoproteins, as we recently found that AML1-ETO, the most frequently occurring acute myeloid leukemia (AML) fusion protein, is not an autophagy substrate. Rather we demonstrate a clear pro-survival role of autophagy in this AML subtype and that addition of autophagy inhibitors in the treatment regimen might be beneficial ...
Autophagy-associated dengue vesicles promote viral transmission avoiding antibody neutralization. - PubMed - NCBIAutophagy-associated dengue vesicles promote viral transmission avoiding antibody neutralization. - PubMed - NCBI
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Autophagy Assays </b> <...Autophagy Assays </b> <...
Autophagy is the process where cells destroy their own components via the lysosomal machinery and recycle them. Innovative Antibodies and Assays are developed to study autophagy mechanisms and identify activators and inhibitors of autophagy.
Flow-cytometric analysis of autophagy in activated primary human CD4+ T cellsFlow-cytometric analysis of autophagy in activated primary human CD4+ T cells
The hallmark of an immune response to Mycobacterium tuberculosis is granuloma formation. CD4+Th1 cells are of central importance in anti-mycobacterial immunity by way of producing effector IFN-γ and TNF-α cytokines that help to contain infection in the granulomas by activating macrophages. The environment of the granuloma is hypoxic and we have little knowledge on CD4+ T cell processes and function in this environment. Autophagy is a de novo intracellular protein and organelle degradation pathway induced in eukaryotic cells by stress-factors such as starvation or hypoxia. It has been described that autophagy is induced in T cells upon activation and autophagic processes might contribute to nutrient supply and the regulation of cytokine production in T cells. The aim of this study was to investigate autophagic processes in CD4+ T cells after activation and the regulation of IFN-γ production under normoxia, and hypoxia as found in the granuloma of TB patients. The main assays, immunoblotting ...
Hypoxia-induced autophagy via the RAGE-KRAS-HIF1α path | Open-iHypoxia-induced autophagy via the RAGE-KRAS-HIF1α path | Open-i
Hypoxia-induced autophagy via the RAGE-KRAS-HIF1α pathway is a survival mechanism in pancreatic tumor cells. (a and b) Indicated Panc02 cells were treated with
AnatomyDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceGeographicals
AutophagyPhagosomesMicrotubule-Associated ProteinsApoptosis Regulatory ProteinsLysosomesUbiquitin-Activating EnzymesTOR Serine-Threonine KinasesClass III Phosphatidylinositol 3-KinasesVacuolesAdenineApoptosisLysosomal-Associated Membrane Protein 2Models, BiologicalSignal TransductionCell Line, TumorSirolimusMembrane ProteinsMitochondrial DegradationCell SurvivalChloroquineMicroscopy, Electron, TransmissionProteolysisCell DeathRNA, Small InterferingMitochondriaEndoplasmic Reticulum StressRNA InterferenceReactive Oxygen SpeciesGene Knockdown TechniquesMultiprotein ComplexesCytoprotectionStarvationNeurodegenerative DiseasesCell LineUbiquitinAdaptor Proteins, Signal TransducingProteasome Endopeptidase ComplexAMP-Activated Protein KinasesStress, PhysiologicalGreen Fluorescent ProteinsEncyclopedias as TopicCytoplasmGermanyOrganellesGlucagon-Like Peptide 2PubMedPeriodicals as TopicBooksPublishingMEDLINESerial Publications
Calorie restrictionCalorie restriction
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 ...
Parkinsons diseaseParkinson's disease
"Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease". Autophagy. 11 (9): 1443-57. doi ...
Endoplasmic-reticulum-associated protein degradationEndoplasmic-reticulum-associated protein degradation
"Autophagy. 4 (2): 141-50. doi:10.4161/auto.5190. PMID 17986870.. *. Vashist S, Ng DT (April 2004). "Misfolded proteins are ...
TFEBTFEB
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 ...
OmegasomeOmegasome
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: ...
Yoshinori OhsumiYoshinori Ohsumi
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.. ...
Heat shock proteinHeat shock protein
They are also involved in special type of autophagy called "chaperone-mediated autophagy", when they enable cytosolic proteins ... Autophagy[edit]. HSPs are involved in classical macroautophagy, when protein aggregates are enclosed by double membrane and ...
NeurodegenerationNeurodegeneration
This can be split into two forms of autophagy: macroautophagy and chaperone-mediated autophagy (CMA).[2] *macroautophagy is ... autophagy-lysosome pathways: a form of programmed cell death (PCD), this becomes the favorable route when a protein is ... chaperone-mediated autophagy defects may also lead to neurodegeneration. Research has shown that mutant proteins bind to the ... Autophagy is essentially a form of intracellular phagocytosis in which a cell actively consumes damaged organelles or misfolded ...
WIPI2WIPI2
The Atg proteins regulate autophagy, which is a lysosomal degradation pathway required for maintaining cell health, surviving ... Autophagy. 6: 506-22. doi:10.4161/auto.6.4.11863. PMID 20505359. Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb ... "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 ...
HSPA8HSPA8
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: ...
MicroautophagyMicroautophagy
... (unlike Macroautophagy and Chaperone-mediated autophagy) is the type of autophagic pathway which is mediated by ... elegans screen identifies autophagy genes specific to multicellular organisms". Cell. 141 (6): 1042-55. doi:10.1016/j.cell. ...
ATG4DATG4D
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 ... This gene belongs to the autophagy-related protein 4 (Atg4) family of C54 endopeptidases. Members of this family encode ... The human ATG4D gene encodes the protein Autophagy related 4D, cysteine peptidase. ...
HDAC6HDAC6
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. doi: ... system and neurodegeneration". Autophagy. 3 (6): 643-5. doi:10.4161/auto.5050. PMID 17912024. Pandey UB, Nie Z, Batlevi Y, ...
AUTEN-67AUTEN-67
... an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects". Autophagy. 12 (2): 273-86. doi: ... AUTEN-67 is an autophagy-enhancing drug candidate that increases autophagic flux in cell lines and in vivo models. It hampers ... 2016). "AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of ...
MAPK15MAPK15
"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 ...
FolliculinFolliculin
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-1 ... "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/ ...
ATG8ATG8
Autophagy is induced upon nutrient depletion or rapamycin treatment and leads to the response of more than 30 autophagy-related ... Autophagy. 1 (2): 119-126. doi:10.4161/auto.1.2.1859. PMID 16874047. Ohsumi, Y. (2001). "Molecular dissection of autophagy: two ... 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 ...
PEX6PEX6
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. PMID 24657987. Waterham HR, Ebberink MS (September 2012). "Genetics and ...
Gaba type a receptor associated protein like 1Gaba type a receptor associated protein like 1
Autophagy. 7 (10): 1098-107. doi:10.4161/auto.7.10.15904. PMID 21597319. Rozenknop A, Rogov VV, Rogova NY, Löhr F, Güntert P, ...
Gladstone InstitutesGladstone Institutes
Autophagy. Researching how autophagy-a process by which cells eliminate abnormal proteins-can help prevent the destruction of ...
HemolysinHemolysin
Mestre MB, Colombo MI (October 2012). "Staphylococcus aureus promotes autophagy by decreasing intracellular cAMP levels". ... Autophagy. 8 (12): 1865-7. doi:10.4161/auto.22161. PMID 23047465. Cavalieri SJ, Snyder IS (September 1982). "Effect of ...
LysosomeLysosome
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 ...
BAG3BAG3
... is involved in chaperone-assisted selective autophagy (CASA). BAG proteins compete with Hip-1 for binding to the Hsc70/ ... This process is called chaperone-assisted selective autophagy (CASA) and is essential for maintaining muscle activity in flies ... 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. ...
Atg1Atg1
AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in S.cerevisiae, encoded by the gene ATG1. It is essential for ... The initiation of autophagy involves the building of the pre-autophagosomal structure (PAS). Most Atg proteins accumulate at ... Of all these, Atg13 has been shown to have roles in both autophagy and Cvt functions; Atg17, 29 and 31 have only functions in ... It is possible that the kinase activity of Atg1 is critical to the magnitude of autophagy but not its initiation. At least, ...
PFKFB3PFKFB3
Likewise, inhibition of PFKFB3 has been found to induce autophagy. See summary image. Autophagy can prolong cellular survival ... "The glycolytic enzyme PFKFB3/phosphofructokinase regulates autophagy". Autophagy. 10 (2): 382-383. doi:10.4161/auto.27345. ISSN ... 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 ...
AnatomyDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceGeographicals
AutophagyPhagosomesMicrotubule-Associated ProteinsApoptosis Regulatory ProteinsLysosomesUbiquitin-Activating EnzymesTOR Serine-Threonine KinasesClass III Phosphatidylinositol 3-KinasesVacuolesAdenineApoptosisLysosomal-Associated Membrane Protein 2Models, BiologicalSignal TransductionCell Line, TumorSirolimusMembrane ProteinsMitochondrial DegradationCell SurvivalChloroquineMicroscopy, Electron, TransmissionProteolysisCell DeathRNA, Small InterferingMitochondriaEndoplasmic Reticulum StressRNA InterferenceReactive Oxygen SpeciesGene Knockdown TechniquesMultiprotein ComplexesCytoprotectionStarvationNeurodegenerative DiseasesCell LineUbiquitinAdaptor Proteins, Signal TransducingProteasome Endopeptidase ComplexAMP-Activated Protein KinasesStress, PhysiologicalGreen Fluorescent ProteinsEncyclopedias as TopicCytoplasmGermanyOrganellesGlucagon-Like Peptide 2PubMedPeriodicals as TopicBooksPublishingMEDLINESerial Publications
Autophagy Flux ChloroquineAutophagy Flux Chloroquine
for Autophagy Flux Assay and LC3 immunostaining Autophagy Autophagy HRP conjugated antibodies are ready-to-use Inhibitors in ... Autophagy Flux Chloroquine. We compared the effect of short- and long-established steatosis on the intensity of autophagy- ... we performed an autophagy flux assay using CQ, which prevents fusion between autophagosomes and lysosomes (Fig. Autophagy is a ... Thus, decreasing autophagy appears to prevent neuronal degeneration The LC3 Antibody Kit for Autophagy includes a rabbit ...
musicaenlamochila.net
Hydroxychloroquine tablets ip hcqs 400, Chloroquine phosphate ginHydroxychloroquine tablets ip hcqs 400, Chloroquine phosphate gin
Chloroquine and autophagy. 11 Ongoing bleeding may have contributed to the increased mortality observed with liberal ...
cadena-azul.es
Autophagy - WikipediaAutophagy - Wikipedia
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 ...
en.wikipedia.org
Autophagy - WikipediaAutophagy - Wikipedia
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 ...
en.wikipedia.org
Autophagy-related protein 13 - WikipediaAutophagy-related protein 13 - Wikipedia
2009). "Atg101, a novel mammalian autophagy protein interacting with Atg13". Autophagy. 5 (7): 973-9. doi:10.4161/auto.5.7.9296 ... Autophagy-related protein 13 also known as ATG13 is a protein that in humans is encoded by the KIAA0652 gene. ATG13 is an ... ATG13 is a target of the TOR kinase signaling pathway that regulates autophagy through phosphorylation of ATG13 and ULK1, and ... Chan EY, Longatti A, McKnight NC, Tooze SA (2009). "Kinase-Inactivated ULK Proteins Inhibit Autophagy via Their Conserved C- ...
en.wikipedia.org
Autophagy ProcessAutophagy Process
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 ...
news-medical.net
Autophagy FunctionsAutophagy Functions
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 ...
news-medical.net
LRRK2 and autophagy in fibroblastsLRRK2 and autophagy in fibroblasts
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 ...
ucl.ac.uk
Autophagy in Neurons. - PubMed - NCBIAutophagy in Neurons. - PubMed - NCBI
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 ...
ncbi.nlm.nih.gov
Autophagy and Stem Cells | SpringerLinkAutophagy and Stem Cells | SpringerLink
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( ...
link.springer.com
Autophagy Research Focus by ProteintechAutophagy Research Focus by Proteintech
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 ...
slideshare.net
Autophagy and aging. - PubMed - NCBIAutophagy and aging. - PubMed - NCBI
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 ...
ncbi.nlm.nih.gov
Processo de AutophagyProcesso de Autophagy
O processo de autophagy foi conservado ao longo do tempo entre todos os organismos vivos. O processo é similar em únicos ... O processo de autophagy foi conservado ao longo do tempo entre todos os organismos vivos. O processo é similar em únicos ... Autophagy está induzido quando a pilha está posta sob o esforço ou há uma prostração de factores e/ou de nutrientes de ... Um dos alvos reguladores na pilha que é estimulada quando autophagy é induzida é o alvo da quinase de proteína do rapamycin ( ...
news-medical.net
Autophagy News, ResearchAutophagy News, Research
Autophagy News and Research. RSS Autophagy is a normal process in which a cell destroys proteins and other substances in its ... Autophagy can help combat Salmonella and other pathogens Autophagy - the process of recycling cellular material in the body, ... Autophagy may prevent normal cells from developing into cancer cells, but it may also protect cancer cells by destroying ... Autophagy is an important biological recycling mechanism that is used to maintain homeostasis within all types of animal tissue ...
news-medical.net
Autophagy는 무엇입니까?Autophagy는 무엇입니까?
Autophagy는 바디에 있는 세포의 파괴를 취급하는 바디에 있는 일반적인 생리적인 프로세스입니다. 그것은 새로운 세포 대형을 위한 파괴한 세포 세포기관의 단백질 강직 그리고 회전율에 의하여 항상성 또는 일반적인 작용을 ... autophagy 워드는 자동 그리스 워드 에서 파생되고 각자를 phagy 의미해 먹기 의미하. ... Autophagy와 긴장. Autophagy는 세포를 영양이 되는 박탈 같이 외부 환경에서 긴장을 살아나는 가능하게 하고 또한 손상한 세포기관의 축적 같이 내부 응력을 및 병원체 또는 전염하는 유기체 내습 저항하는 줍니다. ... Autophagy와 세포 죽음. Autophagy는 또한 세포를 주어진 조건에서 죽입니다. 이들은 프로그램한 세포 죽음의 양식이고 (PCD) autophagic 세포 죽음에게 불립니다. 프로그램된 세포 죽음은 일반적으로 ...
news-medical.net
Postdoc, Autophagy | GenomeWebPostdoc, Autophagy | GenomeWeb
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) ...
genomeweb.com
Autophagy regulates lipid metabolism. - PubMed - NCBIAutophagy regulates lipid metabolism. - PubMed - NCBI
Autophagy regulates lipid metabolism.. Singh R1, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ. ... Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a ... This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human ... A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles ...
ncbi.nlm.nih.gov
Autophagy and hippocampal neuronal injury | SpringerLinkAutophagy and hippocampal neuronal injury | SpringerLink
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 ...
link.springer.com
Pancreas micromanages autophagy | SciencePancreas micromanages autophagy | Science
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 ...
science.sciencemag.org
Autophagy in Hepatic FibrosisAutophagy in Hepatic Fibrosis
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. ...
hindawi.com
JCI - Autophagy and neurodegenerationJCI - Autophagy and neurodegeneration
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 ...
jci.org
Autophagy and Cancer | Hong-Gang Wang | SpringerAutophagy and Cancer | Hong-Gang Wang | Springer
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 ...
springer.com
Role of autophagy in cancer. - PubMed - NCBIRole of autophagy in cancer. - PubMed - NCBI
In this way, autophagy can be viewed as an interruptible path to cell death. d , Cells with defects in apoptosis and autophagy ... a , In apoptosis-defective tumours that are reliant on autophagy to survive metabolic stress, autophagy inhibitors can be used ... In tumour cells with defects in apoptosis, autophagy allows prolonged survival. Paradoxically, autophagy defects are associated ... correction of the autophagy deficiency with autophagy stimulators may delay tumour progression by reducing the rate at which ...
ncbi.nlm.nih.gov
Mackeigan JP mitochondria not autophagy - PubMed - NCBIMackeigan JP mitochondria not autophagy - PubMed - NCBI
Mackeigan JP[Author] AND ("mitochondria"[MeSH Terms] OR "mitochondria"[All Fields])) NOT ("autophagy"[MeSH Terms] OR "autophagy ... Search: Mackeigan JP mitochondria not autophagy *. Format. Summary. Summary (text). Abstract. Abstract (text). MEDLINE. XML. ...
ncbi.nlm.nih.gov
Autophagy: cellular and molecular mechanisms. - PubMed - NCBIAutophagy: cellular and molecular mechanisms. - PubMed - NCBI
Molecular circuitry and signalling pathways regulating autophagy. Autophagy is a complex self-degradative process that involves ... Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and ... Thus, autophagy is generally thought of as a survival mechanism, although its deregulation has been linked to non-apoptotic ... Autophagy is regulated by important signalling pathways in the cell, including stress-signalling kinases such as JNK-1, which ...
ncbi.nlm.nih.gov
AnatomyDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceGeographicals
AutophagyPhagosomesMicrotubule-Associated ProteinsApoptosis Regulatory ProteinsLysosomesUbiquitin-Activating EnzymesTOR Serine-Threonine KinasesClass III Phosphatidylinositol 3-KinasesVacuolesAdenineApoptosisLysosomal-Associated Membrane Protein 2Models, BiologicalSignal TransductionCell Line, TumorSirolimusMembrane ProteinsMitochondrial DegradationCell SurvivalChloroquineMicroscopy, Electron, TransmissionProteolysisCell DeathRNA, Small InterferingMitochondriaEndoplasmic Reticulum StressRNA InterferenceReactive Oxygen SpeciesGene Knockdown TechniquesMultiprotein ComplexesCytoprotectionStarvationNeurodegenerative DiseasesCell LineUbiquitinAdaptor Proteins, Signal TransducingProteasome Endopeptidase ComplexAMP-Activated Protein KinasesStress, PhysiologicalGreen Fluorescent ProteinsEncyclopedias as TopicCytoplasmGermanyOrganellesGlucagon-Like Peptide 2PubMedPeriodicals as TopicBooksPublishingMEDLINESerial Publications
CellularRegulation of autophagyAutophagicFunctions of autophagyMicroautophagyInductionHomeostasisGeneMolecularMitochondriaApoptosis and autophagyCytoplasmicRegulates autophagyPathogensOrganellesLevels of autophagyMechanism of autophagyActivation of autophagyAutophagosome formationNeurodegenerativeRegulateInhibitsRoleRolesSurvivalMachineryTherapeuticStarvation-inducedMutationsProcessATG5Aspects of AutophagyCancer2019CellsMembraneAtg1NeuronalDegradativeBasal autophagy
Cellular51
  • Autophagy allows the orderly degradation and recycling of cellular components. (wikipedia.org)
  • Role in cellular stress - autophagy is a response to cellular stress. (news-medical.net)
  • Autophagy plays an important role in the survival of cellular organisms. (news-medical.net)
  • This is important because, up until now, there hasn't been a clear cellular symptom linked to all these mutations and might indicate that disrupted autophagy is a common feature of LRRK2 mutations. (ucl.ac.uk)
  • 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)
  • Kim KH, Lee MS. Autophagy--a key player in cellular and body metabolism. (springer.com)
  • Autophagy - the process of recycling cellular material in the body, can help combat Salmonella and other pathogens according to researchers at the School of Life Sciences, University of Warwick who have studied how autophagy can get rid of bacteria, and prevent diseases developing. (news-medical.net)
  • 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)
  • Autophagy: cellular and molecular mechanisms. (nih.gov)
  • In addition to elimination of intracellular aggregates and damaged organelles, autophagy promotes cellular senescence and cell surface antigen presentation, protects against genome instability and prevents necrosis, giving it a key role in preventing diseases such as cancer, neurodegeneration, cardiomyopathy, diabetes, liver disease, autoimmune diseases and infections. (nih.gov)
  • The cellular events during autophagy follow distinct stages: vesicle nucleation (formation of the isolation membrane/phagophore), vesicle elongation and completion (growth and closure), fusion of the double-membraned autophagosome with the lysosome to form an autolysosome, and lysis of the autophagosome inner membrane and breakdown of its contents inside the autolysosome. (nih.gov)
  • 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)
  • Normally autophagy acts as a cellular quality-control mechanism. (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)
  • (nature.com)
  • Autophagy fights disease through cellular self-digestion. (nih.gov)
  • Degradation, in particular through autophagy and the proteasome, is important in cellular physiology. (nih.gov)
  • Autophagy is a process of cellular "self-eating" in which portions of cytoplasm are sequestered within double-membrane cytosolic vesicles termed autophagosomes. (nih.gov)
  • Autophagy is a self-degradative process for cellular homeostasis. (eurekalert.org)
  • Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. (nih.gov)
  • The special feature of autophagy process is the formation of double-membrane vesicles called autophagosomes that engulf cellular cargo and deliver them to the vacuole or lysosomes for degradation. (springer.com)
  • J. Beaulaton and R. A. Lockshin, "Ultrastructural study of the normal degeneration of the intersegmental muscles of Antheraea polyphemus and Manduca sexta (Insecta, Lepidoptera) with particular reference to cellular autophagy," Journal of Morphology , vol. 154, no. 1, pp. 39-57, 1977. (hindawi.com)
  • Autophagy is a cellular process that isolates cytoplasmic components that can be directed to the lysosome for degradation. (abcam.com)
  • From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and cytotoxic components. (nih.gov)
  • Autophagy is a conserved dynamic catabolic process, in which nonfunctional macromolecules and cellular organelles are engulfed, degraded, and recycled, thereby playing a crucial role in maintaining cellular homeostasis. (hindawi.com)
  • 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)
  • therefore, autophagy acts as a housekeeping mechanism to maintain cellular homeostasis. (royalsocietypublishing.org)
  • 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)
  • Autophagy, initiated by cellular stress and starvation is the cell s self-repair mechanism and cleaning process by membrane-bound organelles called lysosomes. (medindia.net)
  • Scientists at the ICS-6 investigate the structural biology of cellular autophagy and the interaction of autophagy and viruses. (fz-juelich.de)
  • 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)
  • Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. (elsevier.com)
  • Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. (mdpi.com)
  • Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. (mdpi.com)
  • 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)
  • 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)
  • R. L. Deter, P. Baudhuin, and C. De Duve, "Participation of lysosomes in cellular autophagy induced in rat liver by glucagon," The Journal of Cell Biology , vol. 35, no. 2, pp. (hindawi.com)
  • Autophagy deregulation is a common feature of cancer cells in which has a complex role, showing either an oncogenic or tumor suppressor activity, depending on cellular context and tumor stage. (nature.com)
  • Autophagy is a cellular catabolic process that relies on the cooperation of autophagosomes and lysosomes. (sciencemag.org)
  • We identified 141 candidate genes required for viral autophagy, which were enriched for cellular pathways related to messenger RNA processing, interferon signalling, vesicle trafficking, cytoskeletal motor function and metabolism. (nih.gov)
  • In addition to its cellular homeostasis function, autophagy is emerging as a central component of antimicrobial host defense against diverse infections. (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)
  • Autophagy is a highly conserved cellular process occurring during periods of stress to ensure a cell's survival by recycling cytosolic constituents and making products that can be used in energy generation and other essential processes. (hindawi.com)
  • Autophagy is a highly conserved multistep process that is fundamental to maintain cellular homeostasis. (nature.com)
  • Autophagy (Greek: 'self-eating') was initially identified as a catabolic process for the unselective degradation of cellular content in lysosomes under starvation conditions. (wikipedia.org)
  • Atg8 is one of the key molecular components involved in autophagy, the cellular process mediating the lysosome/vacuole-dependent turnover of macromolecules and organelles. (wikipedia.org)
  • Inhibition of IMPA1 activity can have pleiotropic effects on cellular function, including altering phosphoinositide signalling, autophagy, apoptosis, and other effects. (wikipedia.org)
  • Modulations in Bcl-2, Bcl-xL, and endonuclease G from mitochondria are also thought to play a role in safingol-induced cellular death by regulating autophagy. (wikipedia.org)
  • Autophagy has been shown to play a role in brain health, helping to regulate cellular function. (wikipedia.org)
  • Defects in cellular processes such as autophagy and mitophagy are thought to contribute to the development of diabetic cardiomyopathy. (wikipedia.org)
  • These kinases are tuned to the levels of extracellular nutrients suggesting a coordination in regulation of autophagy and lysomal biogenesis and partnership of two distinct cellular organelles. (wikipedia.org)
Regulation of autophagy5
Autophagic17
  • 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)
  • 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. (nih.gov)
  • We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). (nih.gov)
  • As the number of pathologies associated with defective autophagy increases, emphasis has switched from the mere description of the status of autophagy in these conditions to a more mechanistic dissection of the autophagic changes. (nih.gov)
  • Understanding the reasons behind the autophagic defect, the immediate consequences of the autophagic compromise and how autophagy changes with the evolution of the disease has become a 'must,' especially now that manipulation of autophagy is being considered as a therapeutic strategy. (nih.gov)
  • Autophagic activity is completely abolished in vps34 Δ cells expressing a lipid kinase-dead form of Vps34, indicating that production of PtdIns(3) P is essential for autophagy [ 13 ]. (hindawi.com)
  • B) When autophagy is induced, for example by starvation, there is an increase in all types of autophagic structures. (nih.gov)
  • C) When autophagy is suppressed at any step upstream, none of the autophagic structures are generated. (nih.gov)
  • These vacuoles can be labeled by autophagic marker monodansylcadaverin (MDC), 3-methyladenine (3-MA), an inhibitor of autophagy, was able to inhibit the occurrence of autophagy. (springer.com)
  • Dunn, W. A. Jr., Studies on the mechanisms of autophagy: formation of the autophagic vacuole. (springer.com)
  • In addition, ICP34.5 restricts autophagic initiation and maturation by targeting BECN1, preventing BECN1 autophagy complex formation. (nih.gov)
  • 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)
  • We have isolated 14 autophagy-defective (apg) mutants of the yeast Saccharomyces cerevisiae and examined the autophagic process at the molecular level. (nih.gov)
  • The classic model for autophagy is derived from starvation-induced autophagy where the autophagic machinery is thought to be regulated by a class III phosphatidylinositol 3-kinase (PI3K) complex of which beclin1 is a key player [ 2 , 9 , 10 ]. (hindawi.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)
  • AUTEN-67 is an autophagy-enhancing drug candidate that increases autophagic flux in cell lines and in vivo models. (wikipedia.org)
  • The downstream substrate of Atg1 kinase hasn't been described yet, and it is still a matter of debate as to whether Atg1 primarily acts on autophagy through its kinase activity or through a structural role during autophagic complex formation. (wikipedia.org)
Functions of autophagy6
  • 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)
  • However, in certain experimental disease settings, the self-cannibalistic or, paradoxically, even the prosurvival functions of autophagy may be deleterious. (nih.gov)
  • This Review summarizes recent advances in understanding the physiological functions of autophagy and its possible roles in the causation and prevention of human diseases. (nih.gov)
  • An increased on-rate of autophagy occurs in response to stress signals, resulting in increased autophagosomal and autolysosomal accumulation and successful execution of the adaptive physiological functions of autophagy. (nih.gov)
  • 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)
  • Boya P, Reggiori F, Codogno P (2013) Emerging regulation and functions of autophagy. (springer.com)
Microautophagy1
  • Finally, we provide suggestions for future studies, note where our understanding of the relevant molecular regulators is deficient, and discuss the correlations among PDT-induced resistance and autophagy, especially microautophagy. (springer.com)
Induction12
Homeostasis11
  • 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)
  • Autophagy is an important biological recycling mechanism that is used to maintain homeostasis within all types of animal tissue. (news-medical.net)
  • 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)
  • For example, p70S6 kinase is a substrate of TOR that may act to limit TOR activity, ensuring basal levels of autophagy that are critical for homeostasis. (nih.gov)
  • Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. (nih.gov)
  • Apoptosis and autophagy are both tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease. (nih.gov)
  • Autophagy is a Greek-derived concept that means "self-eating" and is increasingly recognized as an important regulator of homeostasis and disease. (jci.org)
  • Autophagy contributes to the homeostasis of a cell and recently another function of autophagy has been reported. (news-medical.net)
  • The UPR is tailored essentially to reestablish ER homeostasis also through adaptive mechanisms involving the stimulation of autophagy. (hindawi.com)
  • Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. (wikipedia.org)
Gene12
  • Leaf senescence and starvation-induced chlorosis are accelerated by the disruption of an Arabidopsis autophagy gene. (springer.com)
  • show a direct and nutrient-sensitive interaction between the tumor suppressor p53 and the essential autophagy gene Atg7. (sciencemag.org)
  • This volume also includes an explanation of the role of the autophagy-related gene ATG5 in cancer (e.g., gastrointestinal cancer). (elsevier.com)
  • Herein, homozygous deletion of the Sirt1 gene in mice resulted in prostatic intraepithelial neoplasia (PIN) associated with reduced autophagy. (wellnessresources.com)
  • Genome-wide gene expression analysis of Sirt1−/− prostates demonstrated that endogenous Sirt1 repressed androgen responsive gene expression and induced autophagy in the 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)
  • Gene expression analysis further demonstrated that loss of endogenous Sirt1 inhibited autophagy, which regulates normal gland development. (wellnessresources.com)
  • AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in S.cerevisiae, encoded by the gene ATG1. (wikipedia.org)
  • The gene families formerly known as APG, AUT, CVT, GSA, PAZ, and PDD are now unified as the ATG (AuTophaGy related) family. (wikipedia.org)
  • Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. (wikipedia.org)
  • Her major contributions include the discovery of the mammalian autophagy gene, beclin 1 and its role in tumor suppression, longevity, and antimicrobial host defense. (wikipedia.org)
  • Mutations in the EPG5 gene interfere with the autophagy. (wikipedia.org)
Molecular12
  • 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 review summarizes the most up-to-date findings on how autophagy is executed and regulated at the molecular level and how its disruption can lead to disease. (nih.gov)
  • The molecular machinery of autophagy: unanswered questions. (springer.com)
  • Autophagy: from phenomenology to molecular understanding in less than a decade. (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)
  • Mammalian autophagy: core molecular machinery and signaling regulation. (nih.gov)
  • 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)
  • A better understanding of the molecular mechanisms that determine the final outcome of UPR and autophagy activation by chemotherapeutic agents, will offer new opportunities to improve existing cancer therapies as well as unravel novel targets for cancer treatment. (hindawi.com)
  • Thus the molecular description of autophagy is a relatively recent phenomenon (Klionsky and Emr, 2000). (rupress.org)
  • Autophagy is the main mechanism at the molecular level, but evidence has been found for other mechanisms, including inflammation reduction, lipid metabolism, and regulation of cell growth, proliferation and death. (wikipedia.org)
Mitochondria6
Apoptosis and autophagy3
Cytoplasmic6
Regulates autophagy2
  • The Atg14L (Atg14L-Beclin 1-hVps34-p150) and UVRAG (UVRAG-Beclin 1-hVps34-p150) complexes are required for autophagy, whereas the Rubicon complex (Rubicon-UVRAG-Beclin 1-hVps34-p150) negatively regulates autophagy. (nih.gov)
  • To determine whether JFH-1-HCV infection regulates autophagy, we examined the conversion of endogenous LC3 to LC3 II. (pnas.org)
Pathogens8
  • Host defence mechanism - autophagy helps kill cells that are infected or invaded by foreign pathogens. (news-medical.net)
  • A critical role of autophagy in plant resistance to necrotrophic fungal pathogens. (springer.com)
  • 2011). Autophagy differentially controls plant basal immunity to biotrophic and necrotrophic pathogens. (springer.com)
  • 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)
  • In addition, autophagy plays a role in certain diseases, acting to prevent some types of neurodegeneration and cancer, and in the elimination of invading pathogens. (nih.gov)
  • Pathogens and autophagy: Subverti. (mendeley.com)
  • 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)
  • To counteract this mechanism, many pathogens have evolved to evade, subvert, or exploit autophagy. (pnas.org)
Organelles3
Levels of autophagy1
  • Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. (wikipedia.org)
Mechanism of autophagy1
Activation of autophagy3
  • A class III PI3K is needed for activation of autophagy. (nih.gov)
  • Our data demonstrated that UBCS039 induced a time-dependent activation of autophagy in several human tumor cell lines, as evaluated by increased content of the lipidated form of LC3B by western blot and of autophagosomal puncta by microscopy analysis of GFP-LC3. (nature.com)
  • UBCS039-mediated activation of autophagy was strictly dependent on SIRT6 deacetylating activity since the catalytic mutant H133Y failed to activate autophagy. (nature.com)
Autophagosome formation1
  • This review will discuss key findings in autophagy research as well as provide new insights on the role of membrane lipids in autophagosome formation. (hindawi.com)
Neurodegenerative11
Regulate2
  • 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)
  • Other report shows that PPAR α regulate autophagy [ 14 ]. (hindawi.com)
Inhibits3
  • Upstream AMPK activates (), and AKT inhibits (), the autophagy process. (nih.gov)
  • Whereas abrogation of ciliogenesis partially inhibits autophagy, blockage of autophagy enhances primary cilia growth and cilia-associated signalling during normal nutritional conditions. (nih.gov)
  • L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. (nih.gov)
Role37
  • 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)
  • 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)
  • 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)
  • Role of autophagy in cancer. (nih.gov)
  • Role of autophagy in Caenorhabditis elegans. (nih.gov)
  • During Caenorhabditis elegans development, autophagy plays an important role in many physiological processes, including survival under starvation conditions, modulation of life span, and regulation of necrotic cell death caused by toxic ion-channel variants. (nih.gov)
  • The role of autophagy in development and differentiation in mammals. (nih.gov)
  • This study suggests a potential role of autophagy in complement-associated processes that are associated with human diseases. (umassmed.edu)
  • Evidence from several cell types suggests that endocytosis may be coupled to autophagy to a variable extent, and that the amphisome may play a central role as a collecting station for material destined for lysosomal degradation. (nih.gov)
  • Recent advances have helped to define the function of and mechanism for programmed necrosis and the role of autophagy in cell survival and suicide. (nih.gov)
  • Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. (nih.gov)
  • Autophagy has long been considered as a physiological process solely for degradation, but its secretory role has recently emerged. (eurekalert.org)
  • Our findings will open another dimension for therapeutic approaches through the secretory role of autophagy. (eurekalert.org)
  • Recently, autophagy is also reported to play a role in secretion. (eurekalert.org)
  • Deregulation of autophagy plays a pivotal role in the etiology and/or progress of many of these diseases. (nih.gov)
  • 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)
  • The guest editors of this issue are delighted to present this compendium of research articles focusing on the role of oxidative stress and autophagy in metabolism and longevity. (hindawi.com)
  • The recently discovered role of primary cilia in nutrient sensing and signalling motivated us to explore the possible functional interactions between this signalling hub and autophagy. (nih.gov)
  • The functional role of autophagy in the kidneys is also currently under intense investigation although, until recently, evidence showing the involvement of autophagy in the pathogenesis of diabetic nephropathy has been limited. (hindawi.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)
  • Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO. (nih.gov)
  • 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)
  • Codogno, P. and Meijer, A. J., Autophagy and signaling: their role in cell survival and cell death. (springer.com)
  • Volume 9 emphasizes the role of autophagy in diseases, such as leukemia, antifungal and antibacterial immunity, and transplantation. (elsevier.com)
  • 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 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)
  • Professor Heung Kyu Lee from the Graduate School of Medical Science and Engineering and his team found that the autophagy of dendritic cells plays a key role in T-cell activation and they proposed the principles of enhancing anti-cancer effects. (news-medical.net)
  • Professor Lee said, 'This study allowed us to explore the role of autophagy in the anti-cancer immune response of T-cells. (news-medical.net)
  • 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)
  • Our study suggests that autophagy machinery plays a new role in dengue virus transmission. (nih.gov)
  • A research group at Osaka University led by Takeshi Noda discovered that TOR (Target of Rapamycin), an enzyme complex that played a central role in cell growth, controlled autophagy. (news-medical.net)
  • Sirtuin 6 (SIRT6) is a member of the NAD + -dependent class III deacetylase sirtuin family, which plays a key role in cancer by controlling transcription, genome stability, telomere integrity, DNA repair, and autophagy. (nature.com)
  • Interestingly, antioxidants were able to completely counteract UBCS039-induced autophagy, suggesting that ROS burst had a key role in upstream events leading to autophagy commitment. (nature.com)
  • His team was also the first to delineate the role of autophagy in the regulation of synaptic plasticity and behaviour under nutrient deprivation and stress. (wikipedia.org)
  • Because autophagy normally plays a pro-survival role by impeding apoptosis, it is curious that it may play a role in cell death following safingol exposure. (wikipedia.org)
  • The role of reactive oxygen species and autophagy in safingol-induced cell death. (wikipedia.org)
Roles7
Survival10
Machinery4
Therapeutic7
  • Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. (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)
  • 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)
  • These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions. (nih.gov)
  • Therapeutic targeting of autophagy is currently being evaluated in diverse clinical trials but without the benefit of a control engineering perspective. (nature.com)
  • Autophagy is related with a diverse spectrum of diseases and has long been anticipated as a therapeutic option from the point of view of degradation. (eurekalert.org)
  • We provide a systematic review of autophagy and discuss the therapeutic potential of autophagy in diabetic nephropathy to help future investigations in this field. (hindawi.com)
Starvation-induced2
  • Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. (springer.com)
  • Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM (2006) In Situ Detection of Starvation-induced Autophagy. (springer.com)
Mutations1
  • A lot more work is needed in order for us to really understand how mutations in LRRK2 alter autophagy, but this study provides an intriguing hint that autophagy might be very important in Parkinson's disease. (ucl.ac.uk)
Process13
ATG54
  • Systems produce modified complexes Atg8-PE and Atg5-Atg12-Atg16 as autophagy regulators. (hindawi.com)
  • These systems produce modified complexes of autophagy regulators: Atg8-PE and Atg5-Atg12-Atg16, and that may determine the formation and size of the autophagosome. (hindawi.com)
  • This leads to the inactivation of ATG5 and inhibition of autophagy. (wikipedia.org)
  • In response to DNA damage, ATG5 expression is upregulated, increasing autophagy, preventing caspase activation and apoptosis. (wikipedia.org)
Aspects of Autophagy1
  • Before delving into the aspects of autophagy, There ia a well-known answer to the question: What is an autophagy? (hindawi.com)
Cancer13
  • In 1999, a landmark discovery connecting autophagy with cancer was published by Beth Levine's group. (wikipedia.org)
  • To this date, relationship between cancer and autophagy continues to be a main theme of autophagy research. (wikipedia.org)
  • Autophagy may prevent normal cells from developing into cancer cells, but it may also protect cancer cells by destroying anticancer drugs or substances taken up by them. (news-medical.net)
  • 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)
  • for example, some microbes subvert autophagy for replication, and the cytoprotective action can allow cancer cells to resist anti-cancer treatments. (nih.gov)
  • Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression. (sciencemag.org)
  • Aberrations in autophagy are associated with several diseases, including cancer. (mdpi.com)
  • Vazquezmartin A, Oliverasferraros C, Menendez JA (2009) Autophagy facilitates the development of breast cancer resistance to the anti-her2 monoclonal antibody trastuzumab. (springer.com)
  • Thorburn A, Debnath J (2011) Targeting chaperone-mediated autophagy in cancer. (springer.com)
  • However this does not mean that these processes are any less important than MaA, as numerous studies have identified an association between various diseases (Parkinson's disease, Alzheimer's disease, type-II diabetes, obesity, cardiovascular disease, and cancer) and generally unregulated or defective autophagy processes [ 5 - 12 ]. (hindawi.com)
  • Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy. (wikipedia.org)
  • Abgent's antibodies target key areas of research including autophagy, neuroscience, cancer, stem cells and more. (wikipedia.org)
20192
Cells20
  • 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 participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. (hindawi.com)
  • Recent evidence suggests that autophagy provides a protective function to limit tumour necrosis and inflammation, and to mitigate genome damage in tumour cells in response to metabolic stress. (nih.gov)
  • Prolonged starvation and progressive autophagy causes cells to gradually shrink in size but restoration of nutrients allows recovery. (nih.gov)
  • The eventual recruitment of a blood supply cures the tumour of hypoxia and metabolic stress, and the tumour cells formerly surviving through autophagy can emerge to contribute to tumour growth. (nih.gov)
  • 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)
  • The degradation of betaine homo-cysteine methyltransferase (BHMT), a metabolic enzyme, could be used to assess autophagy flux in mammalian cells. (wikipedia.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)
  • Autophagy was also detected in dying Purkinje cells in the cerebellum of lurcher mice. (sciencemag.org)
  • The authors note that inclusion of Bcl2 family members in a complex with the GluRδ2 subunit could provide coordinated regulation of both autophagy and apoptosis in the compromised Purkinje cells of lurcher mice. (sciencemag.org)
  • Apel A, Herr I, Schwarz H, Rodemann HP, Mayer A (2008) Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. (springer.com)
  • Katayama M, Kawaguchi T, Berger MS, Pieper RO (2007) DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. (springer.com)
  • TSC Null Cells Are Aggresome-Defective Despite Abrogated Autophagy. (pnas.org)
  • In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. (nih.gov)
  • We describe here the identification of infectious autophagy-associated dengue vesicles released from infected cells. (nih.gov)
  • Autophagy-deficient donor cells decrease the infection rate of recipients in close-contact co-culture condition. (nih.gov)
  • Higher concentrations of the GO types downregulated the expression of PU.1, a unique transcription factor in monocytes and macrophages, and decreased the conversion of LC3A/B-I to LC3A/B-II, suggesting that PU.1 was associated with autophagy in RAW264.7 cells. (hindawi.com)
  • Tumor cells are killed viva autophagy, rather than apoptosis. (wikipedia.org)
Membrane3
Atg11
  • Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila," Autophagy , vol. 10, no. 3, pp. 453-467, 2014. (hindawi.com)
Neuronal3
  • 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)
  • Activation of hypothalamic autophagy mobilizes neuronal lipids for the controlled availability of neuron-intrinsic FFAs that increase AgRP expression and food intake. (hindawi.com)
Degradative1
Basal autophagy1
  • A) Under normal conditions, basal autophagy occurs. (nih.gov)