The continuous remodeling of MITOCHONDRIA shape by fission and fusion in response to physiological conditions.
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)
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.
Proteolytic breakdown of the MITOCHONDRIA.
The quality of surface form or outline of ORGANELLES.
A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.
The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).
Dominant optic atrophy is a hereditary optic neuropathy causing decreased visual acuity, color vision deficits, a centrocecal scotoma, and optic nerve pallor (Hum. Genet. 1998; 102: 79-86). Mutations leading to this condition have been mapped to the OPA1 gene at chromosome 3q28-q29. OPA1 codes for a dynamin-related GTPase that localizes to mitochondria.
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.
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.
Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
The quantity of volume or surface area of MITOCHONDRIA.
Chemical agents that increase the permeability of CELL MEMBRANES to PROTONS.
The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.
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.
Chemicals with two conjoined aromatic rings incorporating two nitrogen atoms and one of the carbons oxidized with a keto oxygen.
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.
The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell.
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.
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.
A computer simulation developed to study the motion of molecules over a period of time.
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.
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.
The mitochondria of the myocardium.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
The chemical reactions involved in the production and utilization of various forms of energy in cells.
Established cell cultures that have the potential to propagate indefinitely.
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
Proteins involved in the transport of specific substances across the membranes of the MITOCHONDRIA.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
Mitochondria of skeletal and smooth muscle. It does not include myocardial mitochondria for which MITOCHONDRIA, HEART is available.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
"A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics". The EMBO Journal. 25 (15): 3618-26. ... "A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics". The EMBO Journal. 25 (15): 3618-26. ... "Roles of mitochondrial ubiquitin ligase MITOL/MARCH5 in mitochondrial dynamics and diseases". Journal of Biochemistry. 155 (5 ... MITOL is thought to play a protective role against nitrosative stress-mediated disruption of mitochondrial dynamics such as ...
... βIII-tubulin has a GTPase domain which plays an essential role in regulating microtubule dynamics. Differences between Class I ... Congenital neurologic syndromes associated with TUBB3 missense mutations demonstrate the critical importance of class III β- ... "Proteomic characterization of cytoskeletal and mitochondrial class III beta-tubulin". Molecular Cancer Therapeutics. 7 (7): ... The dynamics are normally suppressed by low, subtoxic concentrations of microtubule drugs that also inhibit cell migration. ...
... mitochondrial dynamics, anti-tumor immunity) and their critical contribution to development, progression, and therapy ... Later on, his studies provided the foundation for the rewired signaling in cancer, by demonstrating the important role of ... Ze'ev Ronai studies provide new fundamental understanding for the role and function of epigenetic components (transcription ... "Fine-tuning of Drp1/Fis1 availability by AKAP121/Siah2 regulates mitochondrial adaptation to hypoxia". Molecular Cell. 44 (4): ...
A critical role for the ER in calcium signaling was acknowledged before such a role for the mitochondria was widely accepted, ... Mitochondrial dynamics, the balance between mitochondrial fusion and fission, is an important factor in pathologies associated ... Most mitochondrial genomes are circular. In general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial ... Anti-mitochondrial antibodies Mitochondrial metabolic rates Mitochondrial permeability transition pore Mitophagy Nebenkern ...
... is a family of proteins that play a role in mitochondrial fusion events. This family belongs to the larger Mitochondrial ... These mitochondrial dynamics, first observed over a hundred years ago are important for the health of the cell, and defects in ... The dynamic nature of mitochondria is critical for function. Chen and Chan (2010) have discussed the molecular basis of ... Mitochondrial dynamics in different cells are understood by the way in which these proteins regulate and bind to each other. ...
"Population Critical: How are Caribou Faring?" (PDF). Canadian Parks and Wilderness Society and The David Suzuki Foundation. ... Androgens play an essential role in the antler formation of cervids. The antlerogenic genes in reindeer have more sensitivity ... Flagstad, Oystein; Roed, Knut H (2003). "Refugial origins of reindeer (Rangifer tarandus L) inferred from mitochondrial DNA ... Bergerud, Arthur T. (1996), "Evolving Perspectives on Caribou Population Dynamics, Have We Got it Right Yet?", Rangifer, ...
The role of PKCε acting in non-mitochondrial regions of cardiomyocytes is less well understood, though some studies have ... offering critical mechanistic insights. JM Downey was the first to introduce the role of PKC in cardioprotection against ... It has been demonstrated that altering the dynamics of the (RACK/RACK2) and (RACK1) interaction with PKCε can influence cardiac ... PKCε has also been shown to play a role in modulating mitochondrial permeability transition (MPT); the addition of PKCε to ...
A special role is played by Matrix metalloproteinases. These increase BBB T-cell permeability, specially in the case of MMP-9 ... 2010). "CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies". Int Angiol ... Another development in this area is the finding that some lesions present mitochondrial defects that could distinguish types of ... Critical analysis and first observation in an unselected cohort of MS patients.]". Nervenarzt. 81 (6): 740-6. doi:10.1007/ ...
Das D, Das A, Samanta D, Ghosh J, Dasgupta S, Bhattacharya A, Basu A, Sanyal S, Das Gupta C (August 2008). "Role of the ... The mitochondrial ribosomes of eukaryotic cells functionally resemble many features of those in bacteria, reflecting the likely ... Certain ribosomal proteins are absolutely critical for cellular life while others are not. In budding yeast, 14/78 ribosomal ... Aminoglycosides Biological machines Posttranslational modification Protein dynamics RNA tertiary structure Translation ( ...
"The Role of External and Matrix pH in Mitochondrial Reactive Oxygen Species Generation". Department of Biochemistry and ... "The critical role of Arabidopsis electron-transfer flavoprotein:ubiquinone oxidoreductase during dark-induced starvation". ... Homology modeling, cofactor docking, and molecular dynamics simulation studies". Canadian Institutes of Health Membrane Protein ... Painter HJ, Morrisey JM, Mather MW, Vaidya AB (2007). "Specific role of mitochondrial electron transport in blood-stage ...
Mammalian succinate dehydrogenase functions not only in mitochondrial energy generation, but also has a role in oxygen sensing ... Homology modeling, cofactor docking, and molecular dynamics simulation studies". The Journal of Biological Chemistry. 279 (10 ... Critical Reviews in Biochemistry and Molecular Biology. 50 (2): 168-80. doi:10.3109/10409238.2014.990556. PMC 4653115. PMID ... This occurs in the inner mitochondrial membrane by coupling the two reactions together. Mitochondrial and many bacterial SQRs ...
Finally, we define a critical experiment to determine if our invention is viable. This is a teachable process that we impart to ... The center is focuses on improved diagnosis and treatment for diseases caused by mitochondrial defects. The majority of these ... During the COVID-19 pandemic, the Institute took a lead role and established a clinical testing laboratory, and processed ... The center is focused on developing new revolutionary techniques that reveal the structure and dynamics of biomolecules towards ...
... are in strong agreement with the hypothesis that a recent population expansion of the Okhotsk people played a critical role in ... Studies of Korean mitochondrial DNA lineages have shown that there is a high frequency of Haplogroup D4, ranging from ... and our language phylogeny might also provide a basis for making further inferences about the cultural dynamics of the Ainu ... The mitochondrial-DNA haplogroups of the Han Chinese can be classified into the northern East Asian-dominating haplogroups, ...
Gualberto JM, Mileshina D, Wallet C, Niazi AK, Weber-Lotfi F, Dietrich A (2014). "The plant mitochondrial genome: dynamics and ... In the 1950s and 1960s, John Langridge and George Rédei played an important role in establishing A. thaliana as a useful ... Bundy JG, Davey MP, Viant MR (2009). "Environmental Metabolomics: A Critical Review and Future Perspectives. (Invited Review ... Mitochondrial genome[edit]. The mitochondrial genome of Arabidopsis thaliana is 367,808 base pairs long and contains 57 genes.[ ...
"Role of critical thiol groups on the matrix surface of the adenine nucleotide translocase in the mechanism of the mitochondrial ... Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (Jan 2005). "Nucleolar proteome dynamics". Nature. 433 (7021 ... PPIF is a major component of the mitochondrial permeability transition pore (MPTP) and, thus, highly involved in mitochondrial ... mitochondrial precursor gene: assessment of its role in familial dilated cardiomyopathy". Human Genetics. 105 (6): 582-6. doi: ...
... are in strong agreement with the hypothesis that a recent population expansion of the Okhotsk people played a critical role in ... Analysis of the mitochondrial DNA (mtDNA) of Jōmon skeletons indicates that haplogroups N9b, D4h2, G1b and M7a may reflect ... and our language phylogeny might also provide a basis for making further inferences about the cultural dynamics of the Ainu ... 2004). "Mitochondrial Genome Variation in Eastern Asia and the Peopling of Japan". Genome Research. 14 (10a): 1832-1850. doi: ...
... are in strong agreement with the hypothesis that a recent population expansion of the Okhotsk people played a critical role in ... 2004). "Mitochondrial genome variation in Eastern Asia and the peopling of Japan". Genome Research. 14 (10A): 1832-1850. doi: ... and our language phylogeny might also provide a basis for making further inferences about the cultural dynamics of the Ainu ... 2007). "Mitochondrial DNA sequence variation and phylogenetic analysis in Japanese individuals from Miyazaki prefecture". ...
... are in strong agreement with the hypothesis that a recent population expansion of the Okhotsk people played a critical role in ... revealed by ancient mitochondrial DNA analysis". Journal of Human Genetics. 52 (7): 618-27. doi:10.1007/s10038-007-0164-z. PMID ... and our language phylogeny might also provide a basis for making further inferences about the cultural dynamics of the Ainu ... Little is known about the role of these plants in the economy or if they had dietary or ritual roles. Kisao Ishizuki of the ...
Responsible for Cell Wall Dynamics in Supporting Tissues of Arabidopsis Under Microgravity Conditions and Resist Wall/Role of ... Critical Point (BCAT-3-4-CP) Binary Colloidal Alloy Test - 3: Binary Alloys (BCAT-3-BA) Binary Colloidal Alloy Test - 3: ... 03-24 at the Wayback Machine Protein Crystal Growth-Single Locker Thermal Enclosure System-Crystallization of the Mitochondrial ... Responsible for Cell Wall Dynamics in Supporting Tissues of Arabidopsis Under Microgravity Conditions and Resist Wall/Role of ...
doi:10.1006/jmsc.2000.0714.CS1 maint: multiple names: authors list (link) Boulcott, P. & Wright, P. J. (2008). "Critical timing ... "The role of industrial fisheries and oceanographic change in the decline of North Sea black-legged kittiwakes". Journal of ... "Larval mortality rates and population dynamics of Lesser Sandeel (Ammodytes marinus) in the northwestern North Sea" (PDF). ... dubius and Gymnammodytes semisquamatus by mitochondrial DNA restriction fragment patterns". Fisheries Research. 36 (1): 61-65. ...
Role conflict involves incompatible demands placed upon a person in a manner that makes accomplishing both troublesome. Social ... Järvisalo, J.; Saris, N. E. (1975-09-15). "Action of propranolol on mitochondrial functions--effects on energized ion fluxes in ... Forsyth, D.R. (2010). Group Dynamics (5th Edition). Belmont, CA: Wadsworth. Ross, L., & Ward, A. (1995). Naïve Realism in ... 1963). The effects of threat in bargaining: Critical and experimental analysis. Journal of Abnormal and Social Psychology, 66, ...
... mitochondrial dynamics and functions). Moreover, HMB is cheap (~30- 50 US dollars per month at 3 g per day) and may prevent ... The branched-chain amino acids or BCAAs (leucine, isoleucine, and valine) are critical to this process, in addition to lysine ... Roles in Health and Disease". J. Am. Med. Dir. Assoc. 17 (9): 789-96. doi:10.1016/j.jamda.2016.04.019. PMID 27324808. Studies ... mitochondrial dynamics and functions). Moreover, HMB is cheap (~30- 50 US dollars per month at 3 g per day) and may prevent ...
Okahara F, Itoh K, Nakagawara A, Murakami M, Kanaho Y, Maehama T (Oct 2006). "Critical role of PICT-1, a tumor suppressor ... 2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77-83. doi:10.1038/nature03207. PMID 15635413. S2CID 4344740. Yim JH ... 2007). "GLTSCR2 sensitizes cells to hypoxic injury without involvement of mitochondrial apoptotic cascades". Pathobiology. 74 ( ...
However, it also means that, when intracellular levels of Na+ rise beyond a critical point, the NCX begins importing Ca2+. The ... Due to the delicate role that Ca2+ plays in the contraction of heart muscles, the cellular concentration of Ca2+ is carefully ... ER/mitochondrial Ca2+ uptake and release, and Ca2+ buffering". The Journal of General Physiology. 129 (1): 29-56. doi:10.1085/ ... "Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells". PLOS Biology. 13 (12 ...
Complex I may have a role in triggering apoptosis.[8] In fact, there has been shown to be a correlation between mitochondrial ... "Mitochondrial bioenergetics and dynamics interplay in complex I-deficient fibroblasts". Biochimica et Biophysica Acta. 1802 (5 ... Treatment of the D-form of complex I with the sulfhydryl reagents N-Ethylmaleimide or DTNB irreversibly blocks critical ... Andreazza AC, Shao L, Wang JF, Young LT (April 2010). "Mitochondrial complex I activity and oxidative damage to mitochondrial ...
Li Z, Wang Y, Xue Y, Li X, Cao H, Zheng SJ (Feb 2012). "Critical role for voltage-dependent anion channel 2 in infectious ... VDACs also contain a mitochondrial targeting sequence for the protein's translocation to the outer mitochondrial membrane. In ... Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (Jan 2005). "Nucleolar proteome dynamics". Nature. 433 (7021 ... VDAC2 plays an important role in the mitochondrial cell death pathway transduction hereby regulating apoptotic signaling and ...
The two roles of EF-G in elongation and termination of protein translation are split amongst the mitochondrial elongation ... Li, Wen; Trabuco, Leonardo G.; Schulten, Klaus; Frank, Joachim (2011-05-01). "Molecular dynamics of EF-G during translocation ... the SRL is critical in helping GTPases bind to the ribosome, but is not essential for GTP hydrolysis. There is some evidence to ... G C Atkinson; S L Baldauf (2011). "Evolution of elongation factor G and the origins of mitochondrial and chloroplast forms". ...
Mitofusin-2 (MFN2) is a mitochondrial membrane protein that plays a central role in regulating mitochondrial fusion and cell ... "Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from ... Studying the mechanisms of mitochondrial function, more specifically MFN2 function, during tumorigenesis is critical for the ... Zorzano A, Bach D, Pich S, Palacín M (2004). "[Role of novel mitochondrial proteins in energy balance]". Revista de medicina de ...
Additionally we explore the role of mitochondrial dynamics in critical illness. * Lou Halamek. Professor of Pediatrics ( ... Instructor, Pediatrics - Critical Care. Current Research and Scholarly Interests Our current research is focused on evaluation ... have focused our efforts on the identification of developmental variability in cardiac bioenergetic reserve and mitochondrial ...
ROLE OF DRP1/FIS1-MEDIATED MITOCHONDRIAL FRAGMENTATION IN SEPSIS-INDUCED MYOCARDIAL DYSFUNCTION Society of Critical Care ... However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1- ... Certification in Critical Care Echocardiography: The Evolution of an Emerging PICU Practice PEDIATRIC CRITICAL CARE MEDICINE Su ... P110, an inhibitor of Drp1-Fis1 interaction, abrogated these defects, thus indicating a critical role for this interaction in ...
Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Rubio-Cosials A, Sidow JF, ... ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements ... ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements. 01-05- ... ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements ...
The types of mitochondrial dynamics described include mitochondrial fission and fusion, mitophagy and mitochondrial transport ... As mitochondrial dynamics have a significant influence on homeostasis, in this review, we mainly discuss the role of ... There is evidence that several mitochondrial dynamics-associated proteins, as well as related pathways, have roles in the ... mechanisms need to be better understood in order to propose new therapeutic strategies targeting mitochondrial dynamics that ...
Biology of acute myeloid leukemia stem cells: the role of CITED2 and mitochondrial activity. Mattes, K., 2019, [Groningen]: ... Differential redox-regulation and mitochondrial dynamics in normal and leukemic hematopoietic stem cells: A potential window ... Mattes, K., Vellenga, E. & Schepers, H., 25-Sep-2019, In : Critical Reviews in Oncology/Hematology. 144, 14 p., 102814.. ...
Recent studies have reported that alteration of mitochondrial nucleoid structures induces mitochondrial DNA (mtDNA) release ... Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9- ... In conclusion, our findings reveal a novel mechanism of TAM infiltration in HCC by mitochondrial fission-induced mtDNA stress. ... Here we aimed to investigate whether mitochondrial fission induces mtDNA stress and then promotes TAM infiltration and HCC ...
The authors measured a number of proteins that play a critical role in mitochondrial dynamics and turnover. They found that ... plays a critical role in initiating mitochondrial fission by its translocation from the cytosol to the mitochondrial outer ... Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from ... The recognition of mitochondrial dynamics and trafficking alterations in AD greatly broadens our understanding of mitochondrial ...
Hyperglycemia-induced mitochondrial production of ROS plays a critical role in disease development (9) and disease-associated ... Dysregulation of mitochondrial dynamics is a feature of diabetic disease (7,13,37,39,40). IHG-1 increases mitochondrial fusion ... Balanced mitochondrial fusion and fission are critical in maintaining mitochondrial quality (24,37). The rates of fusion and ... To assess the role of IHG-1 in mitochondrial dynamics, we fluorescently labeled mitochondria by overexpressing mtGFP in ...
ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements. 01-05- ... Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. ... a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for ... A role for tRNA modifications in genome structure and codon usage. Eva Maria Novoa, Mariana Pavon-Eternod, Tao Pan, Lluis Ribas ...
ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements. / ... Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability ... Whereas in cortical primary cultures, Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation ... A role for tRNA modifications in genome structure and codon usage. Eva Maria Novoa, Mariana Pavon-Eternod, Tao Pan, Lluis Ribas ...
The structure and function of the mitochondrial network is regulated by mitochondrial biogenesis, fission, fusion, transport ... A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics. EMBO J 25:3618-3626PubMedCrossRefGoogle ... Chen H, Chan DC (2006) Critical dependence of neurons on mitochondrial dynamics. Curr Opin Cell Biol 18:453-459PubMedCrossRef ... Core proteins of the mitochondrial dynamics machinery play important roles in the regulation of apoptosis, and mutations or ...
"A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics". The EMBO Journal. 25 (15): 3618-26. ... "A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics". The EMBO Journal. 25 (15): 3618-26. ... "Roles of mitochondrial ubiquitin ligase MITOL/MARCH5 in mitochondrial dynamics and diseases". Journal of Biochemistry. 155 (5 ... MITOL is thought to play a protective role against nitrosative stress-mediated disruption of mitochondrial dynamics such as ...
Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the ... Defective Mitochondrial Function and Motility Due to Mitofusin 1 Overexpression in Insulin Secreting Cells Park KS, Wiederkehr ... Developmental Switch of the Serotonergic Role in the Induction of Synaptic Long-term Potentiation in the Rat Visual Cortex Park ... consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal... ...
... obviating a need for morphometric mitochondrial remodeling. The critical role of mitochondrial dynamics factors in hearts, ... Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci U S A. 2012;109:6566-6571. doi: 10.1073/pnas. ... suppressing mitochondrial fission impaired mitochondrial health and increased metrics of apoptosis and mitochondrial ... Mitochondrial fission is frequently considered to be "bad" and mitochondrial fusion to be "good."8,16 By inference, fragmented ...
These results demonstrate that Ryr2 controls mitochondrial Ca2+ dynamics and plays a specific, critical role in promoting ... This manipulation decreased the amplitude and frequency of cytosolic and mitochondrial Ca2+ signals in isolated cardiomyocytes ... mitochondrial metabolism; proteomics; ryanodine receptor; transcriptomics; tricarboxylic acid cycle (TCA cycle) (Krebs cycle). ...
Mitochondrial dysfunction has long been proposed to play a critical role in the pathogenesis of a wide range of microvascular ... Mitochondrial dynamics encompasses 2 complementary processes: mitochondrial fission and fusion (6-9). Mitochondrial fission is ... mitochondrial length, (E) mitochondrial circularity, (F) mitochondrial area, and (G) mitochondrial perimeter. (H) ... Given these conflicted roles of Drp1S600 phosphorylation in mitochondrial fission, we sought to investigate its role in ...
... summarizes recent studies highlighting the molecular pathways that facilitate mitochondria to alter its morphological dynamics ... summarizes recent studies highlighting the molecular pathways that facilitate mitochondria to alter its morphological dynamics ... 2013). A critical regulatory role for macrophage migration inhibitory factor in hyperoxia-induced injury in the developing ... Mitochondrial fusion events are known to play a role in maintaining intact mitochondrial DNA copies, mitochondrial membrane ...
HDAC6 has critical roles in lipid homeostasis and mitochondrial health. The other pathway we investigated is critical in ... HDAC6 not only plays a role in lipid metabolism, but regulates mitochondrial dynamics. Upon glucose-withdrawal, HDAC6 KO cells ... Through this work, we show that two proteins critical in quality control mechanisms also play significant roles in energy ... are critical for DAG accumulation and effective mitochondrial clearance. ...
Mitochondrial dysfunction plays a critical role in the development of chemical and pharmaceutical toxicity. However, current ... By revealing the dynamics of cellular adaptation to mitochondrial damage, this novel organ-on-chip technology permits detection ... The sensor-integrated platform permits real-time tracking of the dynamics of metabolic adaptation to any type of mitochondrial ... "Real-time Monitoring of Metabolic Function in Liver-on-Chip Microdevices Tracks the Dynamics of Mitochondrial Dysfunction," ...
A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics. (PMID: 16874301) Yonashiro R … Yanagi S ... Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a ... Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a ... MARCH5 is a ubiquitin ligase of the mitochondrial outer membrane that plays a role in the control of mitochondrial morphology ...
A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal ... A critical role for the peroxisome proliferator-activated receptor alpha (PPARα) in the cellular fasting response: the PPARα- ... Mitochondrial biogenesis and dynamics in the developing and diseased heart. Genes Dev. 2015;29(19):1981-1991.. View this ... A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid β-oxidation during brown adipocyte ...
PhD in Medical Science at the MRC Mitochondrial Biology Unit). at Medical Research Council (Cambridge), listed on FindAPhD.com ... Elucidating the interplay between mitochondrial dynamics, organelle contact sites and metabolic (re)programming (On the ... Medical Research Council (Cambridge) Mitochondrial Biology Unit * Role and mechanism of mitochondrial transport proteins (On ... Mitochondria house hundreds of biochemical reactions involved in processes critical for the survival and homeostatic adaptation ...
"These data support a critical role for SLC25A46 and mitochondrial dynamics in the establishment and maintenance of neuronal ... SLC25A46 settles on the outer mitochondrial membrane where it regulates mitochondrial dynamics. ... Mutations in the genes associated with mitochondria dynamics OPA1 and MFN2 are linked to similar mitochondrial disorders. ... SLC25A46 unlike typical mitochondrial transporters localizes to the outer mitochondrial membrane.. Middle panels: Visualization ...
3. Mitochondrial dynamics in cancer: Mitochondrial dynamics have been shown to be important for the cellular control of ... In addition, failure to properly maintain this dynamic mitochondrial network has been shown to play a role in a number of ... apoptosis, autophagy and metabolic function, processes that are critical regulators of tumorigenesis. As such, it is essential ... 2. Pathways that regulate mitochondrial dynamics: A number of important cellular processes are accompanied by changes in the ...
M. Sajic, "Mitochondrial dynamics in peripheral neuropathies," Antioxidants & Redox Signaling, 2014. View at: Publisher Site , ... Various experimental observations point towards the critical role of mitotoxicity in the pathophysiology of diabetic neuropathy ... A. P. Rolo and C. M. Palmeira, "Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress," Toxicology ... In addition to disturbed mitochondrial functionality, its dynamics (size, shape, and number) is also known to be affected in ...
... of the role of critical mitochondria fission and fusion genes in the mitochondrial abnormalities induced by Aβ expression will ... News: Abnormal Mitochondrial Dynamics-Early Event in AD, PD? For mitochondrial effects in AD please see our Pharmacogenomics ... News: Abnormal Mitochondrial Dynamics-Early Event in AD, PD? We thank Dr. Zhu for citing our work (Iijima-Ando et al., 2009) in ... News: Abnormal Mitochondrial Dynamics-Early Event in AD, PD? We thank all the commentators on our paper, "Expression of beta ...
Mitochondrial dynamics-mitochondrial fission and fusion in human diseases. N Engl J Med 2013;369:2236-51. doi:10.1056/ ... of mitochondria play critical roles in maintaining functional mitochondria in the presence of environmental stress.60 These ... 22 Mitochondrial dynamics is an important contributor to damage and loss of axons in several neurodegenerative disorders.60 ... Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurol 2015;14:406-19. doi:10.1016 ...
Our study provides evidence for a critical role of DJ-1 in mitochondrial homeostasis by connecting basal autophagy and ... Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinsons disease-associated protein DJ-1. PLoS ... Lehner C, Yakubovich N, O Farrell P. Exploring the role of Drosophila cyclin A in the regulation of S phase. Cold Spring Harb ... Seufert W, Futcher B, Jentsch S. Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins. Nature. 1995; ...
Hu C, Huang Y, Li L. Drp1-dependent mitochondrial fission plays critical roles in physiological and pathological progresses in ... Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from ... referred to as mitochondrial dynamics [17].. Mitochondrial fusion leads to preservation of mitochondrial DNA and transmission ... Perturbing mitochondrial dynamics is often through disturbing the ratio of fusion to fission mitochondrial proteins. Altering ...
... myocardial ischemia/reperfusion injury in rats by regulating mitochondrial dysfunction induced by mitochondrial dynamics ... Cardiovascular Programming During and After Diabetic Pregnancy: Role of Placental Dysfunction and IUGR ... In this study, we have shown that the lipid chaperones FABP4/FABP5 are critical intermediate factors in the deterioration of ... improving mitochondrial activity, mitochondrial membrane potential and ATP content; markedly increasing MFN2 expression and ...
  • In neurodegenerative diseases, neurodegeneration has been related to several mitochondrial dynamics imbalances such as excessive fragmentation of mitochondria, impaired mitophagy, and blocked mitochondria mitochondrial transport in axons. (frontiersin.org)
  • Mitochondria undergoing coordinated cycles of fission and fusion, the balance of fission/fusion events is referred to as the "mitochondrial dynamic. (frontiersin.org)
  • Excessive fragmentation or dysfunction of mitochondria may have an impact on the ATP biogenesis and lead to mitochondrial dysfunction, which can be disastrous for the survival viability of neurons. (frontiersin.org)
  • In this review, three mitochondrial dynamic related events are discussed: the fusion/fission event, movement within the neuronal axon, and disintegration of mitochondria (mitophagy). (frontiersin.org)
  • The vital roles of mitochondria in immunity response have been well documented. (nature.com)
  • Let's put aside for a minute the possibility that mitochondria may actually mediate changes in amyloid, as opposed to the dynamic evaluated in almost all AD modeling studies, which is that Aβ must mediate changes in mitochondrial function. (alzforum.org)
  • IHG-1 must be localized to mitochondria to interact with Mfn1 and Mfn2, and this interaction is necessary for increased IHG-1-mediated mitochondrial fusion. (diabetesjournals.org)
  • IHG-1 is a highly conserved protein localized to mitochondria and plays an important regulatory role in mitochondrial biogenesis by stabilizing the transcriptional cofactor peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) ( 4 ). (diabetesjournals.org)
  • Mitochondria play a central role in cellular adaptation to hyperglycemic conditions ( 7 ). (diabetesjournals.org)
  • Dynamic fusion and fission events are important for the bioenergetic function of mitochondria ( 18 ) as is PGC-1α activity, which plays a key role in enhancing mitochondrial stress-related bioenergetic function ( 19 ). (diabetesjournals.org)
  • Mitochondrial fission relies on another GTPase: cytosolic dynamin-related protein 1 (Drp1), which translocates to mitochondria under circumstances that promote fission to interact with mitochondrial outer membrane protein fission 1 (Fis1) ( 22 ). (diabetesjournals.org)
  • Whereas in cortical primary cultures, Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation in an early phase that can be reversed once the insult has ceased, Mfn2 downregulation intervenes in a delayed mitochondrial fragmentation phase that progresses even when the insult has ceased. (sebbm.es)
  • Downregulation of Mfn2 causes mitochondrial dysfunction, altered calcium homeostasis, and enhanced Bax translocation to mitochondria, resulting in delayed neuronal death. (sebbm.es)
  • Given the facts that MARCH5 regulates the protein proteostasis of Drp1, mitofusin 1, and mitofusin 2 that are pivotal regulators of mitochondrial fusion and fission, MARCH5 is critical for the regulation of standard mitochondria morphology, and deficiencies in it promote cellular senescence. (wikipedia.org)
  • Considering that both Drp1 and MAP1B are substrates for MITOL, MITOL is thought to play a protective role against nitrosative stress-mediated disruption of mitochondrial dynamics such as morphological stability and transport of mitochondria. (wikipedia.org)
  • Conventional wisdom is that mitochondria continuously undergo cyclic fission and fusion, collectively termed mitochondrial dynamism. (ahajournals.org)
  • Although observable in cells having filamentous mitochondria, mitochondrial dynamism is less evident in adult cardiac myocytes. (ahajournals.org)
  • In nonmyocytes, fragmentation of filamentous mitochondria is observed when the balance between mitochondrial fission and fusion is shifted in favor of fission, as during apoptosis. (ahajournals.org)
  • 4 Although these findings support a role for Drp1-mediated mitochondrial fission in cardiac injury, the normal homeostatic function of Drp1 in the comparatively static mitochondria of the adult heart has not been evaluated… until now. (ahajournals.org)
  • The expected consequence of inhibiting Drp1-mediated mitochondrial fission is mitochondrial elongation (from unopposed fusion) and, although quantitative mitochondrial morphometry was not performed, increased numbers of cells having atypically large mitochondria were indeed observed. (ahajournals.org)
  • This review article summarizes recent studies highlighting the molecular pathways that facilitate mitochondria to alter its morphological dynamics, coordinate stress responses, initiate mitophagy and activate cell death in relevance to pulmonary pathologies. (frontiersin.org)
  • The most prominent role for mitochondria is to generate NADH and ATP through the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) ( Dromparis and Michelakis, 2013 ). (frontiersin.org)
  • Upon glucose-withdrawal, HDAC6 KO cells fail to elongate their mitochondria and display increased levels of mitochondrial toxic by-products. (duke.edu)
  • Mitochondria house hundreds of biochemical reactions involved in processes critical for the survival and homeostatic adaptation of the cell. (findaphd.com)
  • Beyond their role in energy production and cellular metabolism, mitochondria are involved in numerous cellular pathways including apoptosis and autophagy, calcium homeostasis, and immunity. (findaphd.com)
  • The main goal of the project is to decipher how the cellular metabolic state modulates these mitochondria-organelle contact sites and their potential interplay with the control of mitochondrial morphology, and vice-et-versa. (findaphd.com)
  • Mitochondria play a large role in human health," said Alexander Abrams, Ph.D. student in Neuroscience at the UM Miller School of Medicine and first author of the study. (miami.edu)
  • Mutations in the genes associated with mitochondria dynamics OPA1 and MFN2 are linked to similar mitochondrial disorders. (miami.edu)
  • Middle panels: Visualization of the inter-connected mitochondrial network by photoactivation of mitochondria in a HeLa cell. (miami.edu)
  • Equal distribution of mitochondria to daughter cells requires that the mitochondrial network undergo fission prior to cell division. (virginia.edu)
  • The mitotic division of mitochondria is a highly regulated process that depends on both the mitochondrial recruitment and phosphorylation of the large GTPase Drp1. (virginia.edu)
  • To that end, we use xenografts of human cancer cell lines and genetically engineered mouse models to determine the role that mitochondria shaping proteins play in the initiation and maintenance of human tumors. (virginia.edu)
  • In our Aβ42 fly brain neurons, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. (alzforum.org)
  • Our examination, through genetic manipulation, of the role of critical mitochondria fission and fusion genes in the mitochondrial abnormalities induced by Aβ expression will be finished soon. (alzforum.org)
  • While studies of apoptotic cell death have defined central regulatory mechanisms including a role for mitochondria, the relationship between core apoptosis factors, mitochondrial physiology, and how this relates to normal and aberrant development remains unsolved. (keystonesymposia.org)
  • Our data showed that inner mitochondrial membrane potential (ΔΨ m ), ATP produced by glycolysis, and, to a lesser degree, ATP produced by mitochondria are critical for maintaining the mitochondrial network, and different metabolic stresses induce distinct morphological patterns (e.g., mitochondrial depolarization is necessary for "donut" formation). (springer.com)
  • Mitochondria play a central role in regulating energy metabolism, redox status and cell death. (keystonesymposia.org)
  • Mitochondria are highly dynamic organelles whose morphology is regulated by cycles of fusion and fission, collectively termed mitochondrial dynamics ( 1 , 2 ). (diabetesjournals.org)
  • Although the functional significance of these changes has not been studied in β-cells, studies of mitochondrial morphology in other cells have demonstrated that the ability of mitochondria to form networks influences both ROS and calcium handling ( 7 - 9 ). (diabetesjournals.org)
  • Due to the central role that mitochondria play as the cellular powerhouse, their unique membrane composition and structure are critical to facilitate a variety of important biochemical processes within the cell. (biophysics.org)
  • Despite their central role in human health and disease, there are no approved drugs that directly target mitochondria. (sciencemag.org)
  • The mitochondria thereby control critical decision points for cells, such as whether to live or die or whether to transform to malignant cancer cells. (sciencemag.org)
  • Despite the central role of mitochondria in human health and disease, there has been no successful therapy for defective mitochondrial function, which is devastating and often fatal. (sciencemag.org)
  • This begs the question: Why is there a void of mitochondria-targeted therapies when its role in human disease is widely recognized? (sciencemag.org)
  • Mitochondrial fusion and fission affect the distribution and quality control of mitochondria. (elifesciences.org)
  • The role of Marf in tethering mitochondria in the ring gland may allow us to better understand how this process affects hormone production and how the different parts of the cell communicate. (elifesciences.org)
  • First, it highlighted the important elucidation of mitochondria morphological changes, mitochondrial membrane potential and structural damage, mitochondrial DNA (mtDNA) damage and reactive oxidative species (ROS) production, etc. (nature.com)
  • Mitochondria play a central role in energy metabolism and even decide the cellular fate. (nature.com)
  • Excessive ROS will destroy the normal structure and function of mitochondria and release from mitochondria via mitochondrial permeability transition pore (mPTP) opening mechanism 5 . (nature.com)
  • This review highlighted the emerging mechanisms related to mitochondrial dysfunction in different fibrotic organs and tissues, including mitochondria morphological changes, mitochondrial membrane potential damage, mitochondrial DNA (mtDNA) damage, ROS production, mitophagy abnormality, mitochondrial transfer, etc. (nature.com)
  • Because ATP supplies in endothelial cells are relatively independent of mitochondrial oxidative pathways, the mitochondria of endothelial cells have been somewhat neglected. (ucl.ac.uk)
  • The mitochondria may also constitute critical "targets" of oxidative stress, because survival of endothelial cells can be compromised by opening of the mitochondrial permeability transition pore or by mitochondrial pathways of apoptosis. (ucl.ac.uk)
  • In addition, evidence suggests that endothelial mitochondria may play a "reconnaissance" role. (ucl.ac.uk)
  • To further understand the underlying cause for the age-associated decrement of mitochondrial density and function in equine skeletal muscle, expression of factors involved in mitochondria biogenesis and mitochondria-selective autophagy pathways, two of the most prominent quality control mechanisms that have been described, were analyzed. (ufl.edu)
  • and 3) the roles of the ubiquitin system at mitochondria and its disease implications. (cancer.gov)
  • Particular areas of cellular focus pertain to the roles of this system in the secretory pathway and at mitochondria, where there are clear associations of the UPS with physiology and disease. (cancer.gov)
  • Surprisingly, under nonstressed conditions, mitochondrial size (fragmentation or enlargement) would seem to be a less important determinant of cardiac phenotype or pathology than the impact that dynamic imbalance has via dysregulated mitochondria quality control, as evidenced by alterations in mitophagy or mitogenesis. (portlandpress.com)
  • Here, we report an unexpected but evolutionarily conserved role for Arf1 and the ArfGEF GBF1 at mitochondria. (embopress.org)
  • The GTPase Arf1 and its GEF GBF‐1/Gea1/2 have a role independent of the well known regulation of vesicle trafficking in maintaining mitochondrial dynamics and function via Cdc48 and mitofusin mediated quality control and ER‐mitochondria contact site functionality. (embopress.org)
  • Prohibitin ring complexes in the mitochondrial inner membrane regulate cell proliferation as well as the dynamics and function of mitochondria. (rupress.org)
  • Lipid profiling by mass spectrometry of GEP-deficient mitochondria reveals a critical role of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells. (rupress.org)
  • Mitochondrial biogenesis therefore requires adjusting and coordinating the assembly of proteins, encoded by both nuclear and mitochondrial genomes, and membrane lipids, some of which are synthesized within mitochondria. (rupress.org)
  • However, although protein transport to mitochondrial membranes has been extensively studied, mechanisms of lipid import into and within mitochondria are only poorly understood. (rupress.org)
  • The effects of TGF-β were mediated by Smad proteins in the mitochondria, rather than in the nucleus, and led to decreased mitochondrial respiration. (sciencemag.org)
  • Mitochondria play an important role in the progression of apoptosis through the release of pro-apoptotic factors, such as cytochrome c, from the mitochondrial intermembrane space. (tcd.ie)
  • These diverse roles of mitochondria are intimately connected to the structure and cellular context of the essential organelle. (biomedcentral.com)
  • Scale bar, 2 μ for (a,b). (c) Like their bacterial ancestors, mitochondria possess two structurally and functionally distinct membranes, the mitochondrial outer and inner membranes (MOM and MIM, respectively). (biomedcentral.com)
  • In addition to creating transportable mitochondrial compartments, mitochondrial division can produce functionally asymmetric daughter mitochondria. (biomedcentral.com)
  • In addition, genetic mutations in Parkin, an E3 ligase, and PINK1, a mitochondrially targeted kinase, lead to impaired mitochondrial dynamics, resulting in altered transport and distribution of mitochondria as well as loss of synaptic function ( Bueler, 2009 ). (jneurosci.org)
  • We show that Ups1 and Gep1 regulate the levels of cardiolipin and phosphatidylethanolamine in mitochondria in a lipid-specific but coordinated manner.Lipid profiling by mass spectrometry of GEP-deficient mitochondria reveals a critical role of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells.We propose that prohibitins control inner membrane organization and integrity by acting as protein and lipid scaffolds. (nih.gov)
  • We offer an array of products for studying the diverse role of mitochondria in various cellular pathways and diseases. (thermofisher.com)
  • As with the OxPhos-specific antibodies, the CellLight® Mitochondria-GFP and -RFP reagents localize to the mitochondria independent of mitochondrial membrane potential (Figures 2 and 3). (thermofisher.com)
  • While connections between the triggering of the unfolded protein response (UPR) and downstream mitochondrial dysfunction are poorly understood, the membranous contacts between the ER and mitochondria, called the mitochondria-associated membrane (MAM), could provide a functional link between these two mechanisms. (thisisms.com)
  • Sahin, Ebrahimi-Fakhari and colleagues studied both rat neurons and patient-derived neurons (created from induced pluripotent stem cells) affected by TSC and used live-cell imaging to examine the distribution and dynamics of mitochondria. (eurekalert.org)
  • Mitochondria play a critical role in axons, and are found in high numbers at presynaptic sites -- the tips of axons that form synapses or junctions with other neurons and release neurotransmitters. (eurekalert.org)
  • Because mitochondria in RGC axons are damaged before cell death, we examined axonal mitochondrial transport dynamics after axonal injury. (arvojournals.org)
  • In the heart, organelles referred to as mitochondria have a critical role in balancing energy production with cellular energetic demand. (grantome.com)
  • Mitochondrial dysfunction mediated through dynamin-related protein 1 (Drp1) propagates impairment in blood brain barrier in septic encephalopathy. (stanford.edu)
  • Mitochondrial dysfunction is an important contributor of sepsis-induced multi-organ system failure. (stanford.edu)
  • More recently, mitochondrial dysfunction in endothelial cells has been implicated in mediating BBB failure in stroke, multiple sclerosis and in other neuroinflammatory disorders. (stanford.edu)
  • Here, we focused on Drp1-mediated mitochondrial dysfunction in endothelial cells as a potential target to prevent BBB failure in sepsis.We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in a cell culture as well as in murine model of sepsis. (stanford.edu)
  • Finally, primary neuronal cultures exposed to LPS were assessed for mitochondrial dysfunction.LPS induced a strong brain inflammatory response and oxidative stress in mice which was associated with increased Drp1 activation and mitochondrial localization. (stanford.edu)
  • P110, an inhibitor of Drp1-Fis1 interaction, abrogated these defects, thus indicating a critical role for this interaction in mediating sepsis-induced brain dysfunction. (stanford.edu)
  • Finally, LPS mediated a direct toxic effect on primary cortical neurons, which was abolished by P110 treatment.LPS-induced impairment of BBB appears to be dependent on Drp1-Fis1-mediated mitochondrial dysfunction. (stanford.edu)
  • Inhibition of mitochondrial dysfunction with P110 may have potential therapeutic significance in septic encephalopathy. (stanford.edu)
  • Due to the essential nature of mitochondrial functions, excessive mitochondrial fission leads to brain dysfunction. (frontiersin.org)
  • Nevertheless, the present findings provide strong support for mitochondrial dysfunction and impaired mitochondrial dynamics in AD. (alzforum.org)
  • In Parkinson's disease (PD), oxidative stress and mitochondrial dysfunction underlie the development of neuropathology. (springer.com)
  • Compensatory mechanisms may also occur in mice lacking PINK1 that, in contrast to cells and Drosophila , have only mild mitochondrial dysfunction and lack dopaminergic neuron loss. (springer.com)
  • 1 Accordingly, inhibition of mitochondrial fission mediated by the fission-promoting protein Drp1 limits postischemic cardiac injury, 2 , 3 in which programmed cardiomyocyte cell death is thought to contribute to long-term heart dysfunction. (ahajournals.org)
  • Mitochondrial dysfunction plays a critical role in the development of chemical and pharmaceutical toxicity. (technologynetworks.com)
  • The study, entitled "Real-time Monitoring of Metabolic Function in Liver-on-Chip Microdevices Tracks the Dynamics of Mitochondrial Dysfunction," appears in the Proceedings of the National Academy of Sciences. (technologynetworks.com)
  • Recent evidence has established the deregulation of mitochondrial dynamics in response to metabolic dysfunction and diseases. (findaphd.com)
  • Our results indicate that Aβ42-induced mitochondrial mislocalization contributes to Aβ42-induced neuronal dysfunction in vivo. (alzforum.org)
  • Iijima-Ando K, Hearn SA, Shenton C, Gatt A, Zhao L, Iijima K . Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease . (alzforum.org)
  • Disruption of fusion results in mitochondrial heterogeneity and dysfunction. (springer.com)
  • Mitochondrial dysfunction, which originates from primary defects within the organelle or is induced by environmental stresses, plays a critical role in human disease. (sciencemag.org)
  • A long-standing hypothesis is that defective energy supply and/or excessive ROS generation accounts for the pathology caused by mitochondrial dysfunction. (sciencemag.org)
  • There is growing evidence that mitochondrial dysfunction contributes to the development and progression of fibrosis. (nature.com)
  • The heart, liver, kidney and lung are highly oxygen-consuming organs that are sensitive to mitochondrial dysfunction. (nature.com)
  • Moreover, the fibrotic process of skin and islet is closely related to mitochondrial dysfunction as well. (nature.com)
  • This review summarized emerging mechanisms related to mitochondrial dysfunction in different fibrotic organs and tissues above. (nature.com)
  • Therefore, with gaining the increasing knowledge of mitochondrial structure, function, and origin, we could kindle a new era for the diagnostic and therapeutic strategies of many fibrotic diseases based on mitochondrial dysfunction. (nature.com)
  • Mitochondrial dysfunction could induce fibrotic diseases. (nature.com)
  • What are the mechanisms of mitochondrial dysfunction in fibrosis? (nature.com)
  • When mitochondrial dysfunction occurs, the normal cellular biological processes are disrupted, and the oxygen homeostasis is destroyed in tissue. (nature.com)
  • In this damaging microenvironment, mitochondrial dysfunction usually occurs, which is closely related to the development of fibrotic diseases 8 . (nature.com)
  • Mitochondrial dysfunction seems to play a major role in the pathology of ALS. (kclifesciences.org)
  • More recent investigations into APAP hepatotoxicity have established the critical role of mitochondrial dysfunction in mediating liver injury as well as clarified mechanisms of APAP-induced hepatocyte cell death. (ingentaconnect.com)
  • highlight the role of DsbA-L on mitochondrial dysfunction of tubular cells in diabetic kidney and provide a novel therapeutic insight to alleviate diabetic tubulopathy via targeting mitochondrial dynamics. (portlandpress.com)
  • A significant association has been observed between the dysfunction of mitochondrial and many types of cancer. (dovepress.com)
  • Mitochondrial dysfunction is a factor in a myriad of pathophysiological conditions, including age-related neurodegenerative disorders, cancer, metabolic syndrome, and cardiovascular disease. (routledge.com)
  • The information in this volume is critical to those developing mitochondrion-targeted therapies aimed at assuaging mitochondrial dysfunction or the specific factors contributing to its dysfunction. (routledge.com)
  • Acute silencing of Ran in various tumor cell types causes aberrant mitotic spindle formation, mitochondrial dysfunction, and apoptosis. (aacrjournals.org)
  • Thus, these PD-linked mutations are consistent with the idea that axonal dysfunction plays an early and significant role in the disorder. (jneurosci.org)
  • Therefore, we investigated whether the guanosine triphosphatase (GTPase) Rab32, a known regulator of the MAM, mitochondrial dynamics, and apoptosis, could be associated with ER stress as well as mitochondrial dysfunction. (thisisms.com)
  • CONCLUSIONS: ER stress is strongly associated with Rab32 upregulation in the progression of MS, leading to mitochondrial dysfunction and neuronal death. (thisisms.com)
  • 7 Indeed, mitochondrial dysfunction causes various ocular diseases such as Leber's hereditary optic neuropathy, dominant optic atrophy, and normal tension glaucoma. (arvojournals.org)
  • Diabetic stress increases the production of reactive oxygen species (ROS), leading to mitochondrial fragmentation and dysfunction. (sciencemag.org)
  • Conversely, overexpression of IHG-1 leads to increased mitochondrial fusion and also protects cells from reactive oxygen species-induced apoptosis. (diabetesjournals.org)
  • Mitochondrial fusion ensures mixing of organelle components, ensures preservation of mitochondrial membrane potential, protects against oxidant stress and apoptosis, and allows for optimal bioenergetic function ( 23 - 27 ). (diabetesjournals.org)
  • Core proteins of the mitochondrial dynamics machinery play important roles in the regulation of apoptosis, and mutations or abnormal expression of these factors are associated with inherited and age-dependent neurodegenerative disorders. (springer.com)
  • Suen DF, Norris KL, Youle RJ (2008) Mitochondrial dynamics and apoptosis. (springer.com)
  • 9 , 10 Unexpectedly, Ikeda et al 5 found the opposite: suppressing mitochondrial fission impaired mitochondrial health and increased metrics of apoptosis and mitochondrial permeability transition pore opening. (ahajournals.org)
  • Research in the last decade has revealed that mitochondrial fusion and fission impact nearly every aspect of mitochondrial function, from cellular metabolism, to calcium homeostasis, to the control of cell survival through apoptosis and autophagy. (virginia.edu)
  • Mitochondrial dynamics have been shown to be important for the cellular control of apoptosis, autophagy and metabolic function, processes that are critical regulators of tumorigenesis. (virginia.edu)
  • Transmission electron microscopy showed that I/R caused outer mitochondrial membrane rupture, cristae disappearance and vacuolation, while vitexin reduced mitochondrial damage and ultimately reduced cardiomyocyte apoptosis. (medworm.com)
  • The meeting will focus on the relationship between apoptosis regulatory pathways, mitochondrial physiology, metabolism, and non-apoptotic death mechanisms in the context of normal development and pathological situations including degenerative disorders and cancer. (keystonesymposia.org)
  • Another is the BCL-2 protein BAX, which has been long recognized for its permeabilization of the outer mitochondrial membrane during apoptosis and that we have discovered also plays a critical role in regulating necrosis through distinct mechanisms involving mitochondrial dynamics (fission-fusion) (PNAS, 2012). (yu.edu)
  • Interestingly, manipulations that shift the dynamic balance to favor fusion are able to prevent mitochondrial fragmentation, maintain mitochondrial dynamics, and prevent apoptosis. (diabetesjournals.org)
  • CONCLUSIONS These data suggest that alterations in mitochondrial fusion and fission play a critical role in nutrient-induced β-cell apoptosis and may be involved in the pathophysiology of type 2 diabetes. (diabetesjournals.org)
  • In addition, exposure to high levels of glucose and/or free fatty acid has been shown to affect β-cell viability by inducing mitochondrial apoptosis and has been linked to ROS-induced mitochondrial calcium overload and damage ( 13 ). (diabetesjournals.org)
  • With ischemia/reperfusion (I/R) of the heart, fission is enhanced and is associated with mitochondrial swelling, depolarization, and production of reactive oxygen species (ROS), as well as apoptosis. (portlandpress.com)
  • Whether remodelling of mitochondrial networks is necessary for apoptosis-associated cytochrome c release, or merely an accompanying process, has been a subject of debate. (tcd.ie)
  • Here we discuss evidence for and against the role of mitochondrial fragmentation in the progression of apoptosis and highlight recent advances which indicate that mitochondrial fission is not a critical requirement for apoptosis-associated cytochrome c release. (tcd.ie)
  • We also discuss an emerging role for Bcl-2 family members as regulators of mitochondrial fission and fusion dynamics, independent of the role of this family in the regulation of apoptosis. (tcd.ie)
  • Signal transducer and activator of transcription 3 (STAT3) modulates a variety of genes involved in the regulation of critical functions, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, and immunity. (bvsalud.org)
  • We hypothesized that muscle IM would activate the ubiquitin-proteolysis, autophagy-lysosome (mitophagy) pathway, mitochondrial dynamics remodelling and apoptosis partially controlled by the FoxO signalling pathway. (elsevier.com)
  • Conclusion: Our data indicate that IM-induced mitochondrial deterioration is associated with altered protein expressions in the autophagic/mitophagic pathway, more fragmented mitochondrial network and activation of apoptosis partly under the influence of FoxO3 activation. (elsevier.com)
  • BACKGROUND: Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. (thisisms.com)
  • Herein, we summarize studies that address the multi-modal role of Zn dyshomeostasis in breast cancer with respect to the role of Zn in modulating oxidative stress, DNA damage response/repair pathways and cell proliferation/apoptosis, and the relationship to aberrant regulation of Zn transporters. (mdpi.com)
  • Irreversible decreased axonal mitochondrial transport velocity may be useful to predict RGC apoptosis after axonal injury. (arvojournals.org)
  • Induced in high glucose-1 (IHG-1) is a conserved mitochondrial protein associated with diabetic nephropathy (DN) that amplifies profibrotic transforming growth factor (TGF)-β1 signaling and increases mitochondrial biogenesis. (diabetesjournals.org)
  • Hyperglycemia, oxidative stress, and TGF-β1 signaling induce increased mitochondrial biogenesis and alterations in mitochondrial dynamics ( 11 - 17 ). (diabetesjournals.org)
  • The structure and function of the mitochondrial network is regulated by mitochondrial biogenesis, fission, fusion, transport and degradation. (springer.com)
  • This high-capacity energy transduction system is the result of a remarkable surge in mitochondrial biogenesis and maturation during the fetal-to-adult transition in cardiac development. (jci.org)
  • In this Review, we describe the role of specific nuclear receptors and their coregulators in the dynamic control of mitochondrial biogenesis and energy metabolism in the normal and diseased heart. (jci.org)
  • The biogenesis of this high-capacity mitochondrial system occurs largely during the perinatal stage of development. (jci.org)
  • Bragoszewski P, Turek M, Chacinska A. Control of mitochondrial biogenesis and function by the ubiquitin-proteasome system. (springer.com)
  • Our data suggest that mitochondrial content and biogenesis markers were reduced in aged TRI, and that autophagic activity was impaired in both muscles with age, albeit more pronounced in the TRI muscle. (ufl.edu)
  • In line with compromised myogenic potential of aged muscle-derived satellite cells, there were age-related alterations in mitochondrial biogenesis and autophagy pathways, with satellite cells derived from TRI being more susceptible to impairments with age. (ufl.edu)
  • Thus, we hypothesize that oxaloacetate will prolong survival of ALS model mice by activating mitochondrial biogenesis. (kclifesciences.org)
  • Title: The cytosolic cochaperone Sti1 is relevant for mitochondrial biogenesis and morphology. (nih.gov)
  • It harbors the multisubunit complexes of the respiratory chain, key enzymes of many catabolic and anabolic pathways, and various protein translocases with crucial roles during mitochondrial biogenesis. (rupress.org)
  • These results suggest that resveratrol Tegobuvir (GS-9190) plays a pivotal role in the mitochondrial biogenesis machinery that may provide a protective mechanism counteracting seizure-induced neuronal damage by activation of the PGC-1 signaling pathway. (bx-912.com)
  • Open in a separate window Physique 2 Involvement of mitochondrial biogenesis in kainic acid (KA)-induced status epilepticus in hippocampal CA3 subfield. (bx-912.com)
  • Concomitant with changes in mitochondrial and cardiac morphology was decreased expression of nuclear and mitochondrial transcription factors which collectively play a critical role in mitochondrial biogenesis. (grantome.com)
  • The recessive Parkinsonism-linked genes PTEN - induced kinase 1 ( PINK1 ) and Parkin maintain mitochondrial integrity by regulating diverse aspects of mitochondrial function, including membrane potential, calcium homeostasis, cristae structure, respiratory activity, and mtDNA integrity. (springer.com)
  • It is localized in the mitochondrial outer membrane and has four transmembrane domains. (wikipedia.org)
  • There are four mitochondrial compartments: the outer mitochondrial membrane (OMM), intermembrane space (IMS), inner mitochondrial membrane (IMM) and the matrix with inner membrane folds called cristae. (frontiersin.org)
  • This is referred to as mitochondrial membrane potential (Δψm). (frontiersin.org)
  • But unlike the majority of human SLC25 family members (there are 53) that transport molecules across the inner mitochondrial membrane, SLC25A46 settles on the outer mitochondrial membrane where it regulates mitochondrial dynamics. (miami.edu)
  • SLC25A46 unlike typical mitochondrial transporters localizes to the outer mitochondrial membrane. (miami.edu)
  • localizing a variable polyT mutation in the translocase of the outer mitochondrial membrane as a diagnostic predictor of risk for AD. (alzforum.org)
  • A dose-dependent decrease in cell viability was observed during CoCl 2 treatment along with increases in mitochondrial membrane potential and generation of reactive oxygen species (ROS). (medsci.org)
  • Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. (springer.com)
  • Recent studies indicate that nutrient-induced ROS increases subcellular mitochondrial membrane potential (ΔΨmt) heterogeneity and fragmentation of the mitochondrial architecture ( 14 , 15 ). (diabetesjournals.org)
  • It is typically found within mitochondrial membranes, where it is known to modulate membrane structure and dynamics. (biophysics.org)
  • Importantly, disruption of the membrane structure, either through increase or decrease of cardiolipin concentration in the membrane, is known to play a central role in a variety of diseases, including cancer. (biophysics.org)
  • Hence, understanding how membrane structure and dynamics are affected by cardiolipin composition is of immediate importance to multiple areas of research. (biophysics.org)
  • Among the atomistic model renderings, the centrally placed cardiolipin molecule emphasizes its role in our study and displays the lipid's unique structure, while the overhead views of the bilayer patches with cardiolipin featured in orange (other lipids in green) embody the key focus in our study on exploring how changing the concentration of cardiolipin altered membrane properties. (biophysics.org)
  • Newer-generation compounds that bear positive charges [for example, MitoQ ( 5 )] and/or have high affinity to the mitochondrial membrane lipids ( 6 ) are now in clinical trials ( Table 1 ). (sciencemag.org)
  • In mammals, Mitofusin 1 (Mfn1) and Mitofusin 2 (Mfn2) regulate outer mitochondrial fusion whereas inner membrane fusion is controlled by Optic atrophy protein 1 (Opa1). (elifesciences.org)
  • these dynamic membrane processes are critical for mitochondrial health. (asbmb.org)
  • Drp1 is a soluble GTPase that splits the mitochondrial membrane. (asbmb.org)
  • Mitofusin and Opa1 are integral membrane GTPases that work together to fuse the mitochondrial membranes. (asbmb.org)
  • CL is synthesized in the mitochondrial inner membrane, or IM, and a fraction of CL is transported to the OM. (asbmb.org)
  • PA changes the mitochondrial membrane's biophysical properties and facilitates mitofusion-mediated membrane fusion . (asbmb.org)
  • All M1 groups exhibited modestly attenuated I/R-induced mitochondrial ROS levels and swelling, and preserved mitochondrial membrane potential. (portlandpress.com)
  • The small GTPase Arf1 plays critical roles in membrane traffic by initiating the recruitment of coat proteins and by modulating the activity of lipid‐modifying enzymes. (embopress.org)
  • MARCH5, also known as membrane-associated ring finger (C3HC4) 5, is an E3 ubiquitin-protein ligase that is localized in the mitochondrial outer membrane, which is involved in the regulation of mitochondrial morphology through ubiquitination of dynamin-related protein (DMN1L), mitofusin-1 (MFN1), and mitofusin 2 (MFN2) that are pivotal regulators of mitochondrial fission and fusion. (dovepress.com)
  • The mitochondrial inner membrane is considered to be the most protein-rich cellular membrane, whose functional impairment is associated with aging, myopathies, and neurological disorders in humans ( Chan, 2006 ). (rupress.org)
  • The uptake of mitochondrion-selective dyes is dependent on the mitochondrial membrane potential. (thermofisher.com)
  • These dyes thereby enable researchers to probe mitochondrial activity, localization, and abundance, as well as to monitor changes in membrane potential in response to pharmacological agents that alter mitochondrial function. (thermofisher.com)
  • Combine targeting sequence-fluorescent protein fusion with the transduction efficiency of BacMam to label organelles independently of function (i.e., pH, mitochondrial membrane potential). (thermofisher.com)
  • Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. (uni.lu)
  • While KMO is localized to the outer mitochondrial membrane in eukaryotic organisms, no mitochondrial role for KMO has been described. (prolekarniky.cz)
  • Neurons initially strive to extrude high and potentially toxic cytosolic Ca 2+ by increasing the activity of plasma membrane ion pumps [ 3 , 7 ], and by sequestering Ca 2+ in the mitochondrial matrix, depolarising the mitochondrial membrane potential, Δψ m [ 8 ]. (plos.org)
  • Ca 2+ that entered through TRPM2 induced lysosomal membrane permeabilization, which led to the release of lysosomal Zn 2+ and a subsequent increase in mitochondrial Zn 2+ . (sciencemag.org)
  • Mitofusin (Mfn) 1 and 2 are two recently-discovered mitochondrial-shaping proteins that are found on the outer membrane and are major regulators of mitochondrial architecture. (grantome.com)
  • We focus on the impaired mitophagy pathway represented by PINK/parkin defects in neurodegenerative diseases, the important role of the ubiquitin protease system (UPS), and the potential connection between mitochondrial dynamics and the pathological process of neurodegenerative diseases. (frontiersin.org)
  • Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. (sebbm.es)
  • Together with two other recent reports that cardiac-specific deletion of Drp1 perturbs mitophagy, these findings point to modulation of targeted mitochondrial elimination as a major quality control function for Drp1, and possibly other mitochondrial dynamism factors, in the heart. (ahajournals.org)
  • Three nearly simultaneous descriptions of cardiac-specific Drp1 gene deletion mice, one of which is published in this edition of Circulation Research , 5 have revealed not only that Drp1 is essential for normal cardiac function but also that its primary effect may be on autophagy/mitophagy rather than on structural mitochondrial remodeling. (ahajournals.org)
  • The investigators were careful to draw a clear distinction between mitochondrial involvement in macroautophagy and mitophagy mediated by the canonical PINK-Parkin mechanism, 8 which they did not specifically interrogate. (ahajournals.org)
  • Parkin, a cytoplasmic E3 ubiquitin ligase, is involved in mitochondrial quality control pathways, including mitochondrial fission and mitophagy by autophagy-related genes. (springer.com)
  • It was demonstrated that overexpression of USP30 triggers the mitochondrial dynamic signaling toward elevated fusion and reduced fission and halts mitochondrial clearance via mitophagy. (springer.com)
  • Bordi M, Nazio F, Campello S. The close interconnection between mitochondrial dynamics and mitophagy in cancer. (springer.com)
  • Second, it introduced the abnormality of mitophagy and mitochondrial transfer also contributed to the fibrotic process. (nature.com)
  • PGAM5 regulates multiple aspects of mitochondrial function, including mitophagy. (kclifesciences.org)
  • Notably, cinnabar genetically interacts with the Parkinson's disease associated genes Pink1 and parkin , as well as the mitochondrial fission gene Drp1 , implicating KMO in mitochondrial dynamics and mitophagy, mechanisms which govern the maintenance of a healthy mitochondrial network. (prolekarniky.cz)
  • Transwell cultures of brain microvascular endothelial cells co-cultured with astrocytes were used to assess the effect of LPS on expression of tight-junction proteins, mitochondrial function, and permeability to fluorescein isothiocyanate (FITC) dextran. (stanford.edu)
  • There is evidence that several mitochondrial dynamics-associated proteins, as well as related pathways, have roles in the pathological process of neurodegenerative diseases with an impact on mitochondrial functions and metabolism. (frontiersin.org)
  • Characteristic hallmarks in the brains of patients with neurodegenerative diseases such as the accumulation of a-synuclein, hyperphosphorylated tau, and amyloid beta (Aβ) plaques, have been proven to be related to the activity of mitochondrial fission proteins. (frontiersin.org)
  • The authors measured a number of proteins that play a critical role in mitochondrial dynamics and turnover. (alzforum.org)
  • Bolender N, Sickmann A, Wagner R, Meisinger C, Pfanner N (2008) Multiple pathways for sorting mitochondrial precursor proteins. (springer.com)
  • MARCH5 is also involved in the removal of proteins associated with specific neurodegenerative disorders such as ataxin-3 in Machado-Joseph disease or mSOD1 in amyotrophic lateral sclerosis likely supporting mitochondrial function. (wikipedia.org)
  • Mitochondrial fission and fusion proteins are highly expressed in myocardium. (ahajournals.org)
  • Through this work, we show that two proteins critical in quality control mechanisms also play significant roles in energy homeostasis. (duke.edu)
  • This mitochondrial developmental maturation process occurs in parallel with well-characterized changes in the expression of contractile apparatus isoforms, ion channels, and calcium handling proteins. (jci.org)
  • The new findings suggest that the SLC25A46 and Ugo1 proteins may play similar roles. (miami.edu)
  • Several proteins are known to play a role in this process, including the kinases Cdk1 and Aurora A, the small GTPase RalA, and the large, multifunctional protein RalBP1. (virginia.edu)
  • Mitochondrial fusion, which was assessed by measuring the expression of proteins optic atrophy protein 1 (OPA1) and mitofusin 2 (Mfn2), declined due to CoCl 2 exposure, but B355252 addition was able to elevate Mfn2 expression while OPA1 expression was unchanged. (medsci.org)
  • Manipulations of key mitochondrial dynamics proteins OPA1, DRP1, and Fis1 were tested for their role in β-cell mitochondrial morphology. (diabetesjournals.org)
  • Parkin mediates the covalent addition of ubiquitin (Ub) chains to Lys 6, Lys 11, and Lys 63 on diverse mitochondrial-related target proteins. (springer.com)
  • Functional characterisation of this variant in fibroblasts, from one living affected individual, revealed impaired mitochondrial network and function as well as disrupted levels of known interacting proteins such as XPA. (bmj.com)
  • Ubiquitination also affects the trafficking of proteins within the cell, activates signal transduction pathways, modulates gene expression, and plays critical roles in DNA repair. (cancer.gov)
  • Lastly, I developed AKAP9-null and AKAP9F/F mice as tools for studying the roles of AKAP9 proteins in organism development and disease. (vanderbilt.edu)
  • Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. (uni.lu)
  • High cytosolic [Ca 2+ ] is bound by an EF hand motif within Miro proteins, resulting in mitochondrial arrest. (thisisms.com)
  • The human brain work is particularly welcome, as it provides both message- and protein-level data for genes and their protein products that mediate mitochondrial fission (Drp and Fis1) and fusion (Mfn1, Mfn2, Opa1, and Tomm40). (alzforum.org)
  • Fis1, the receptor for DRP1, was also increased, and mitochondrial fusion peptides (mitofuscins and OPA1) were reduced. (alzforum.org)
  • Mitochondrial fusion relies on dynamin-related GTPases, mitofusins (Mfns) 1 and 2, and optic atrophy 1 (OPA1) ( 20 , 21 ). (diabetesjournals.org)
  • Furthermore, using a combination of biochemistry, molecular genetics and cell biology, we investigate how these pathways interact with the core mitochondrial fusion and fission machinery, the large fission GTPase Drp1, and the fusion-mediating GTPases Mfn1, Mfn2 and Opa1. (virginia.edu)
  • Our laboratory studies mitochondrial division and fusion , focusing on three mechanochemical dynamin-related GTPases: Drp1, mitofusin and Opa1. (asbmb.org)
  • Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1. (uni.lu)
  • Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. (uni.lu)
  • Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. (uni.lu)
  • In addition, mitochondrial phospholipids play important roles in regulation of mitochondrial dynamics. (asbmb.org)
  • Next, I examined the mitochondrial targeting of AKAP350C and its role in the regulation of mitochondrial dynamics and stress response. (vanderbilt.edu)
  • Human MARCH5 is a mitochondrial localized E3 ubiquitin-protein ligase that is critical for the regulation of mitochondrial dynamics. (dovepress.com)
  • These molecules are implicated in several processes, including adult hippocampal neurogenesis, neuronal firing activity, the formation of the synaptic cleft, the enhancement of neuronal plasticity, and the regulation of mitochondrial dynamics [ 1 , 2 ]. (hindawi.com)
  • Similarly, mitochondrial defects mediated via Drp1-Fis1 interaction in primary microvascular endothelial cells were associated with increased BBB permeability and loss of tight-junctions after acute LPS injury. (stanford.edu)
  • The relationship between the expression of mitochondrial fission key regulator dynamin-related protein 1 (Drp1) and the percentage of CD163 (a marker of TAMs)-positive cells was investigated in HCC tissues using immunohistochemistry. (nature.com)
  • Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization. (nature.com)
  • Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming. (sebbm.es)
  • The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition impairs both mitochondrial fragmentation and generation of iPS cell colonies. (sebbm.es)
  • Taken together, our data indicate that mitochondrial fission controlled by an Erk-Drp1 axis constitutes an early and necessary step in the reprogramming process to pluripotency. (sebbm.es)
  • MARCH5 promotes ubiquitination of Drp1 and a knockdown of MARCH5 is by RNAi led to abnormal mitochondrial fusion. (wikipedia.org)
  • The researchers linked mitochondrial abnormalities induced by Drp1 deficiency to increased mitochondrial content and impaired autophagy, including decreased autophagic mitochondrial clearance. (ahajournals.org)
  • MAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death. (findaphd.com)
  • Mitochondrial fission, measured by phosphorylated dynamin-related protein 1 (p-DRP1) and fission protein 1 (FIS1) expression, also decreased following CoCl 2 exposure, and was stabilized by B355252 addition. (medsci.org)
  • Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. (springer.com)
  • Overexpression of human KMO in mammalian cells finds that KMO plays a role in the post-translational regulation of DRP1. (prolekarniky.cz)
  • Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. (sebbm.es)
  • From a pathological perspective, in a neuronal cell model, dominant-negative MARCH5 prevents mitochondrial fragmentation during neurodegenerative stress induced by the neuron-specific reactive oxygen generator 6-hydroxydopamine, the complex I inhibitor rotenone or Alzheimer's-related amyloid beta peptide. (wikipedia.org)
  • These findings suggest that mitochondrial fragmentation-defragmentation might play a role in the effects of noxious stimuli. (diabetesjournals.org)
  • The high circulating glucose concentrations characteristic of diabetes induce the excessive production of reactive oxygen species (ROS), which triggers mitochondrial fragmentation. (sciencemag.org)
  • to investigate the role of this channel in mitochondrial fragmentation in endothelial cells, which become dysfunctional in diabetics. (sciencemag.org)
  • The increase in mitochondrial Zn 2+ led to the recruitment of the fission factor Drp-1, resulting in mitochondrial fragmentation. (sciencemag.org)
  • This pathway may play a role in the pathology of aging-associated diseases that are characterized by increased mitochondrial fragmentation. (sciencemag.org)
  • We hypothesized that ROS-sensitive TRPM2 channels mediated diabetic stress-induced mitochondrial fragmentation. (sciencemag.org)
  • This signaling pathway may operate in aging-associated illnesses in which excessive mitochondrial fragmentation plays a central role. (sciencemag.org)
  • A better understanding of the relationship between the specific changes in mitochondrial dynamics/turnover and cell death will be instrumental to identify potentially neuroprotective pathways steering PINK1-deficient cells towards survival. (springer.com)
  • Such pathways may be manipulated in the future by specific drugs to treat PD and perhaps other neurodegenerative disorders characterized by abnormal mitochondrial function and dynamics. (springer.com)
  • The goals of our research are: (1) to uncover the molecular mechanisms that directly control mitochondrial dynamics, (2) to identify and characterize signaling pathways that interact with the mitochondrial dynamics machinery and (3) to determine how these interactions impact the pathology of diseases such as cancer. (virginia.edu)
  • A number of important cellular processes are accompanied by changes in the mitochondrial network, but the signaling pathways that link these processes to the mitochondrial fusion and fission machinery are not well understood. (virginia.edu)
  • Using unbiased approaches such as large-scale proteomic and RNAi screens, as well as more targeted gain- and loss-of-function analyses, we are identifying and characterizing signaling pathways that regulate mitochondrial fusion and fission. (virginia.edu)
  • As such, it is essential that we understand the molecular basis of how various oncogenic signaling pathways converge upon the fusion and fission machinery and how mitochondrial dynamics contribute to oncogenic transformation and tumorigenesis. (virginia.edu)
  • Although mounting lines of evidences reveal the pivotal role of Parkin in mitochondrial quality control pathways, the crucial role of deubiquitinases including the USP30 deubiquitinase is emerging. (springer.com)
  • With contributions from an impressive cadre of internationally recognized scientists, the book discusses coordinated mitochondrial functions that regulate cell function by discrete signaling pathways. (routledge.com)
  • Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. (hindawi.com)
  • In recent years, several reports have suggested a new role for Wnt signaling as a regulator of metabolic pathways [ 9 , 10 ]. (hindawi.com)
  • Progress has been made in identifying the molecular machineries that carry out these events and the signaling pathways that integrate mitochondrial behavior with cell physiology. (keystonesymposia.org)
  • Su investigación va dirigida por un lado en determinar el papel de Mfn2 y su relevancia en el control de la morfología mitocondrial y la viabilidad neuronal bajo condiciones de excitotoxicidad. (sebbm.es)
  • A well-maintained balance of these processes (mitochondrial dynamics) is essential for neuronal signaling, plasticity and transmitter release. (springer.com)
  • These data support a critical role for SLC25A46 and mitochondrial dynamics in the establishment and maintenance of neuronal processes. (miami.edu)
  • It has essential roles during embryonic development, particularly for neuronal and muscular functions. (bmj.com)
  • Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. (hindawi.com)
  • Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders. (hindawi.com)
  • in particular, mitochondrial fission happens as an early event in the apoptotic process and results in neuronal cell death in various cerebral insults [9,10]. (bx-912.com)
  • Several studies, including ours, showed that seizure-affected mitochondrial fission expression with neuronal damage and alteration of mitochondrial dynamic protein expression can provide a protective effect opposing seizure-induced hippocampal neuronal damage [5,11,12]. (bx-912.com)
  • In this issue of Circulation Research, Ikeda et al describe a central function for the mitochondrial fission protein, Dynamin-related protein 1 (Drp-1), in macroautophagy and mitochondrial autophagy. (ahajournals.org)
  • However, not much is known about age-related changes in mitochondrial function in equine skeletal muscle. (ufl.edu)
  • However, we still have much to learn regarding the coordinate regulation of the activities that drive the context-specific changes in mitochondrial form and function. (biomedcentral.com)
  • Mitochondrial electron transport chain (ETC) comprises five large protein complexes embedded across the IMM responsible for OXPHOS system. (frontiersin.org)
  • Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. (genecards.org)
  • We present possible new druggable targets in mitochondrial biology, including protein modification, calcium ion (Ca 2+ ) transport, and dynamics, as we move into a new era of mitochondrial medicine. (sciencemag.org)
  • The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. (edu.au)
  • Background The HERC2 gene encodes a 527 kDa E3 ubiquitin protein ligase that has key roles in cell cycle regulation, spindle formation during mitosis, mitochondrial functions and DNA damage responses. (bmj.com)
  • Home » Laboratory of Protein Dynamics and Signaling » Allan M. Weissman, M.D. (cancer.gov)
  • Using a presequence-containing model protein and a site-directed photo-crosslinking approach, we identified the cytosolic chaperones Hsp70 (Ssa1) and Hsp90 (Hsp82) as well as their cochaperones, Sti1 and Ydj1, as putative cytosolic factors involved in mitochondrial protein import. (nih.gov)
  • Collectively, these data suggest that GSNOR may act as a longevity protein countering defects in mitochondrial physiology that arise from age-related epigenetic deregulation. (pnas.org)
  • The matrix houses the circular mitochondrial genome (mtDNA), which encodes protein components of the respiratory complexes I to IV. (biomedcentral.com)
  • Useful for both live-cell imaging and fixed-cell analyses, these CellLight® reagents are prepackaged BacMam expression vectors encoding a fluorescent protein (GFP or RFP) fused to the leader sequence of the mitochondrial protein E1α-pyruvate dehydrogenase. (thermofisher.com)
  • If brain Aβ oligomers are toxic because they disrupt mitochondrial physiology in general, and the fission-fusion apparatus specifically, then preventing the responsible associations is a reasonable therapeutic approach. (alzforum.org)
  • Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting "Mitochondrial Dynamics and Physiology", which will share a keynote address and two plenary sessions with this meeting. (keystonesymposia.org)
  • The molecular mechanism underpinning skeletal-muscle physiology points toward an essential role for STIM1-controlled SOCE to drive Ca 2+ /calcineurin/nuclear factor of activated T cells (NFAT)-dependent morphogenetic remodeling programs and to support adequate sarcoplasmic-reticulum (SR) Ca 2+ -store filling. (springer.com)
  • These experiments will provide a comprehensive top-down analysis of mitofusin function in the adult mammalian myocardium, linking the intact heart phenotype, isolated cardiac myocyte physiology, and mitochondrial respiration and dynamics. (grantome.com)
  • However, specific pathological mechanisms need to be better understood in order to propose new therapeutic strategies targeting mitochondrial dynamics that have shown promise in recent studies. (frontiersin.org)
  • The mechanisms of mitochondrial dynamics cause an imbalance in several neurodegenerative diseases and allow us to have a better understanding of the pathogenesis, while altered peripheral blood mitochondrial dynamics provide a potential diagnostic approach for Alzheimer's disease. (frontiersin.org)
  • Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. (sebbm.es)
  • Tilokani L, Nagashima S, Paupe V, Prudent J. Mitochondrial dynamics: overview of molecular mechanisms. (findaphd.com)
  • This adds significant new insights into the mechanisms by which the Pink1/parkin pathway regulates mitochondrial morphology and function. (alzforum.org)
  • Damage of the CNS tissue appears to be amplified by mechanisms that are in part shared by the two conditions and involve oxidative burst activation in microglia/macrophages, mitochondrial damage and axonal energy failure, Wallerian degeneration and meningeal inflammation. (bmj.com)
  • The homeostasis of mitochondrial function is maintained by multiple mechanisms, collectively called mitochondrial quality control mechanisms. (keystonesymposia.org)
  • Our laboratory studies fundamental mechanisms of cell death and the roles of cell death in normal biology and human disease. (yu.edu)
  • In addition, the discovery of the role of mitochondrial dynamics and autophagy in APAP-induced liver injury provides additional insight into the elaborate cell signaling mechanisms involved in the pathogenesis of this important clinical problem. (ingentaconnect.com)
  • In spite of these new insights into the mechanisms of liver injury, significant controversy still exists on the role of innate immunity in APAP-induced hepatotoxicity. (ingentaconnect.com)
  • Thus, identification of novel molecular mechanisms leading to metastatic growth of GC cells is critical for the development of new therapeutic targets for treatment of this malignancy. (dovepress.com)
  • Great progress has been made in our understanding of the molecular mechanisms that actively shape the dynamic mitochondrial network. (biomedcentral.com)
  • This review will highlight recent advances in our understanding of the molecular mechanisms that impact mitochondrial form and the integration of these mechanisms with one another and with cellular function. (biomedcentral.com)
  • Among these categories, deregulated mechanisms contributing to increased oxidative stress and consequent genomic instability play an important role in the development of a variety of human diseases, including breast cancer [ 3 , 4 ]. (mdpi.com)
  • ROS target various mechanisms that contribute to diabetes-associated diseases, among which mitochondrial dynamics is emerging as an important disease mechanism ( 7 , 8 ). (sciencemag.org)
  • The molecular mechanisms that regulate mitochondrial function are gradually being uncovered, but the critical link between mitochondrial morphology and oxidative capacity is unknown. (grantome.com)
  • These mice will be used to investigate mitofusins in post-natal cardiac growth and to explore mechanisms by which mitochondrial morphology affects mitochondrial content and respiratory function. (grantome.com)
  • To date, networking activity, and its role in mediating β-cell mitochondrial morphology and function, remains unclear. (diabetesjournals.org)
  • We also offer a range of mitochondrion-selective dyes with which to monitor mitochondrial morphology and function. (thermofisher.com)
  • Left panels: High resolution microscope images showing the donut shaped outer mitochondrial membranes. (miami.edu)
  • however, there are lingering doubts about whether cardiolipin directly contributes to structural differences between inner and outer mitochondrial membranes. (biophysics.org)
  • In addition, there are questions about how natural fluctuations in cardiolipin concentration alter the structure and dynamics of those membranes. (biophysics.org)
  • In our study, we use atomistic molecular dynamics simulations to explore how changing the concentration of cardiolipin alters the structure and lipid dynamics of model mitochondrial membranes. (biophysics.org)
  • Binding to PA restrains the assembled machinery from initiating the constriction of the mitochondrial membranes, likely creating a priming step for mitochondrial division. (asbmb.org)
  • Yeast Arf1 co‐fractionated with ER and mitochondrial membranes and interacted genetically with the contact site component Gem1. (embopress.org)
  • Arf1 interacts with the AAA‐ATPase Cdc48, which removes misfolded Fzo1 from mitochondrial membranes. (embopress.org)
  • In diabetes, increased glucose metabolism resulting in increased mitochondrial production of reactive oxygen species (ROS) is believed to be the primary event leading to the development and progression of diabetic vascular complications ( 8 ). (diabetesjournals.org)
  • During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. (sebbm.es)
  • While age as a risk factor is a common point between these types of pathology, there are other similarities, such as the interaction between lipid metabolism and mitochondrial health. (duke.edu)
  • HDAC6 not only plays a role in lipid metabolism, but regulates mitochondrial dynamics. (duke.edu)
  • The results showed that even at low troglitazone concentrations previously regarded as safe, in which traditional tests don't reveal any damage to the cells, the new liver-on-chip technology was able to detect mitochondrial stress that forces the liver to increase its reliance on glucose metabolism. (technologynetworks.com)
  • As will be described, members of the nuclear receptor transcription factor superfamily serve to dynamically control preference and capacity for cardiac mitochondrial fuel metabolism during development and in response to myriad physiologic conditions. (jci.org)
  • More specific keywords: Mitochondrial dynamics, Metabolism, Cell fate decision. (findaphd.com)
  • Several antioxidants or compounds aimed at boosting energy metabolism, through improving ATP production, have been tested clinically to improve mitochondrial function but have yielded disappointing or inconclusive results ( Table 1 ) ( 1 - 4 ). (sciencemag.org)
  • This implies that processes such as ADME (absorption, distribution, metabolism and excretion) that are typically involved in type A adverse drug reactions, may have a role in hypersensitivity reactions too. (doabooks.org)
  • While accumulating studies are focused on the roles of glucose and amino acid metabolism in facilitating pluripotency, little is known regarding the role of lipid metabolism in regulation of stem cell activities. (embopress.org)
  • Accumulation of mitochondrial damage is commonly accepted as an age-related phenomenon associated with the inescapable side effects of oxidative metabolism. (pnas.org)
  • The acid-mediated tumor invasion hypothesis proposes altered glucose metabolism and increased glucose uptake, observed in the vast majority of clinical cancers by fluorodeoxyglucose-positron emission tomography, are critical for development of the invasive phenotype. (aacrjournals.org)
  • We propose that this altered glucose metabolism and flux in malignant cells plays a critical role in cancer biology ( 15 - 17 ). (aacrjournals.org)
  • The enzyme kynurenine 3-monooxygenase (KMO) operates at a critical branch-point in the kynurenine pathway (KP), the major route of tryptophan metabolism. (prolekarniky.cz)
  • The authors did a marvelous job in providing biochemical and cell biological evidence linking the Pink1/parkin pathway to mitochondrial autophagy. (alzforum.org)
  • Regulation of mitochondrial function by chaperone-mediated autophagy (submitted). (yu.edu)
  • The other pathway we investigated is critical in neurodegenerative disease, Parkinson's disease. (duke.edu)
  • Different data support a role for the epidermal growth factor receptor (EGFR) pathway during liver regeneration and hepatocarcinogenesis. (sebbm.es)
  • In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. (hindawi.com)
  • These findings reveal a novel mitochondrial role for KMO, independent from its enzymatic role in the kynurenine pathway. (prolekarniky.cz)
  • IHG-1 forms complexes with known mediators of mitochondrial fusion-mitofusins (Mfns) 1 and 2-and enhances the GTP-binding capacity of Mfn2, suggesting that IHG-1 acts as a guanine nucleotide exchange factor. (diabetesjournals.org)
  • Here, we show that Mfn2 is the only member of the mitochondrial fusion/fission machinery whose expression is reduced in in vitro and in vivo models of excitotoxicity. (sebbm.es)
  • En el presente trabajo hemos estudiado la relevancia de Mfn2 no solamente en el mantenimiento de la morfología y el buen funcionamiento de las mitocondrias en excitotoxicidad, sino también en la viabilidad de las neuronas. (sebbm.es)
  • USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2. (springer.com)
  • To address this possibility, we will, for the first time, examine the role of mitofusins in the development of pathological and physiological cardiac hypertrophy and characterize the differential effects of Mfn1 and/or Mfn2 ablation in the adult cardiac myocyte. (grantome.com)
  • In particular, we have focused our efforts on the identification of developmental variability in cardiac bioenergetic reserve and mitochondrial oxidative stress in the setting of sepsis. (stanford.edu)
  • Brain cytokines levels, oxidative stress markers, and activity of mitochondrial complexes were measured using biochemical assays. (stanford.edu)
  • Soubannier V, McBride HM (2009) Positioning mitochondrial plasticity within cellular signaling cascades. (springer.com)
  • By revealing the dynamics of cellular adaptation to mitochondrial damage, this novel organ-on-chip technology permits detection of chemical toxicity before any effects on cell or tissue viability can be observed. (technologynetworks.com)
  • This body of work investigates the roles of AKAP350 splice variants in cellular stress response. (vanderbilt.edu)
  • An essential resource for life and health scientists as well as pharmaceutical industry professionals, this volume highlights the importance of mitochondrial signaling and its role in establishing a harmonized communication between several cellular compartments. (routledge.com)
  • On the other hand, the global changes associated with neoplastic transformation raise the possibility that critical cellular processes may be "qualitatively" different in tumor cells, relying on effector molecules that are mutated, amplified, or otherwise differentially expressed in cancer, as opposed to normal tissues. (aacrjournals.org)
  • Maintaining the shape of this complex network is critical for both mitochondrial and cellular function and involves the activities of mitochondrial division, fusion, motility, and tethering. (biomedcentral.com)
  • Mitochondrial division and fusion serve to create a compartment that is a connected conductor, able to mix its contents and have access to mtDNA and its products, but able to be distributed to distant cellular destinations via motor-dependent transport on actin or microtubule networks. (biomedcentral.com)
  • In silico simulations using mathematical models provide testable predictions concerning the morphology and cellular and extracellular dynamics at the tumor-host interface. (aacrjournals.org)
  • At this stage, organization of microtubules and distribution of synaptic vesicle markers were not significantly altered, suggesting that mitochondrial mislocalization occurs without global axonal transport defects. (alzforum.org)
  • Programmed cell death plays a critical role during development and adult homeostasis by eliminating unneeded and damaged cells, and defects in cell death can result in a wide range of diseases. (keystonesymposia.org)
  • Similarly, mitochondrial defects were observed in mammalian and yeast cells. (embopress.org)
  • These OxPhos-specific antibodies are versatile tools for investigating mitochondrial morphogenesis, as well as for characterizing degenerative diseases such as Alzheimer's disease and Parkinson's disease that are associated with defects in mitochondrial function. (thermofisher.com)
  • Rab32 connects ER stress to mitochondrial defects in multiple sclerosis. (thisisms.com)
  • Of note, these mitochondrial bioenergetics defects have been related to PD. (mdpi.com)
  • Recent studies have reported that alteration of mitochondrial nucleoid structures induces mitochondrial DNA (mtDNA) release into the cytosol, which is recognized as mtDNA stress, and consequently regulates innate immunity. (nature.com)
  • Three-dimensional reconstructions of mitochondrial images at glial lamina of DBA/2J obtained by an electron microscope revealed that alteration of mitochondrial dynamics induced by elevated IOP is involved in glaucoma. (arvojournals.org)
  • However, they are emerging as agents with diverse roles in modulating the dynamics of intracellular calcium and the generation of reactive oxygen species and nitric oxide. (ucl.ac.uk)
  • No doubt future studies will further clarify AD mitochondrial fission-fusion function and resolve these details. (alzforum.org)
  • Together, these findings indicate that IHG-1 is a novel regulator of both mitochondrial dynamics and bioenergetic function and contributes to cell survival following oxidant stress. (diabetesjournals.org)
  • Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. (sebbm.es)
  • We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal. (koreamed.org)
  • The equilibrium between mitochondrial fusion/fission, as well as the organelle motility, determine network morphology and ultimately mitochondrial/cell function. (springer.com)
  • The combined effects of free fatty acid and glucose on β-cell survival, function, and mitochondrial morphology were explored with relation to alterations in fusion and fission capacity. (diabetesjournals.org)
  • instead, they monitored mitochondrial function as an indicator of indirect effects of the treatments. (sciencemag.org)
  • Selected clinical trials on drugs affecting mitochondrial function. (sciencemag.org)
  • Here, we will focus on the role of STIM1 in skeletal-muscle structure, development and function. (springer.com)
  • Skeletal muscle aerobic capacity, mitochondrial function and regenerative capacity have been found to decline with age in humans and rodents. (ufl.edu)
  • Equine skeletal muscle aging was accompanied by a shift in fiber type composition towards a higher percentage of type I and IIA muscle fibers, decrease in mitochondrial density and cytochrome c oxidase activity, but preserved mitochodnrial respiratory function. (ufl.edu)
  • We have identified a highly conserved motif in PGAM5 that is critical for both the formation of multimeric complexes and for robust phosphatase activity, suggesting that formation of multimeric PGAM5 complexes is critical for the biological function of PGAM5. (kclifesciences.org)
  • Previous studies demonstrate that Dlg is critical for development of normal synapse structure and function, as well as for normal synaptic Scrib localization. (jneurosci.org)
  • Ongoing studies are oriented towards determining the roles played by these regions in E3 function and in identifying specific substrates. (cancer.gov)
  • Loss of function of ARF‐1 or GBF‐1 impaired mitochondrial morphology and activity in Caenorhabditis elegans . (embopress.org)
  • The ArfGEF GBF‐1/Gea1/2 and Arf1 are required for mitochondrial dynamics and function from yeast to man. (embopress.org)
  • Loss and gain-of-function experiments identified Sox4 as a critical activator of PI3K/AKT and MAPK signaling in ALL cells. (biomedsearch.com)
  • Wnt ligands are critical for the correct function of the central nervous system. (hindawi.com)
  • Research reveals that these processes impact mitochondrial function in healthy and apoptotic cells and cause inherited neuropathies in humans when disturbed. (keystonesymposia.org)
  • en] Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. (uni.lu)
  • A series of experimental evidence supports that α-synuclein physiological action is relevant for mitochondrial homeostasis, while its pathological aggregation can negatively impinge on mitochondrial function. (mdpi.com)
  • Taken together, this work reveals that cell-autonomous fatty acid production is required for proper dendritic development and establishes the role of SREBP in complex neurons for dendrite elaboration and function. (sdbonline.org)
  • As mitochondrial dynamics have a significant influence on homeostasis, in this review, we mainly discuss the role of mitochondrial dynamics in several neurodegenerative diseases. (frontiersin.org)
  • Therefore, HDAC6 has critical roles in lipid homeostasis and mitochondrial health. (duke.edu)
  • Thus, Arf1 is involved in mitochondrial homeostasis and dynamics, independent of its role in vesicular traffic. (embopress.org)
  • This system of ~50 cytokines and ~20 receptors plays a particularly prominent role in development, homeostasis and activation of leukocytes in the mammalian immune system. (keystonesymposia.org)
  • Here we report that inhibition of endogenous IHG-1 expression results in reduced mitochondrial respiratory capacity, ATP production, and mitochondrial fusion. (diabetesjournals.org)
  • The small GTPase Ran plays a pivotal role in the process of spindle formation ( 9 ) by releasing target molecules ( 10 , 11 ) that promote microtubule stability, especially TPX2 ( 12 ), from inhibition by importin α/β receptors ( 13 ). (aacrjournals.org)
  • Indeed, direct inhibition of a mitochondrial electron transport chain complex in CD4 + T cells was sufficient to inhibit IFN-γ production. (sciencemag.org)
  • Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders. (uni.lu)
  • Abnormal Mitochondrial Dynamics-Early Event in AD, PD? (alzforum.org)
  • Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. (koreamed.org)
  • Proper response to stress is critical for cell and organism survival. (vanderbilt.edu)
  • however recent research has uncovered a central role for these organelles in cell signaling, cell survival, and cell death. (routledge.com)
  • Role of CaMKIV and its targets in stem cell biology: Using genetic knockout mouse models, we reported a role for CaMKIV in the control of hematopoietic stem cell (HSC) proliferation and survival. (iu.edu)
  • 5 Thus, axonal transport plays a critical role in RGC survival, and its failure may be associated with glaucomatous optic neuropathy. (arvojournals.org)
  • As such, it is critical to understand the pathogenesis of disease where aging is the main risk factor. (duke.edu)
  • Finally, we propose possible future research directions for mitochondrial dynamics and consider the challenge of translating promising therapeutic targets toward the dual goals of symptom relief and disease modification in Neurodegenerative diseases. (frontiersin.org)
  • In addition, failure to properly maintain this dynamic mitochondrial network has been shown to play a role in a number of diseases, including Parkinson's disease, Alzheimer's disease, diabetes and cancer. (virginia.edu)
  • One promising redox therapeutic from Edison Pharmaceuticals is EPI-743 ( 7 , 8 ), a designed CoQ10 analog with much more potent antioxidant activity, and is being tested currently in pediatric patients with various mitochondrial diseases, including Rett syndrome, Friedreich's ataxia, and Leigh syndrome ( Table 1 ). (sciencemag.org)
  • Thus, it is not surprising that aberrant mitochondrial architecture has been associated with an ever-increasing number of diseases. (biomedcentral.com)
  • The current challenge for researchers and clinicians is to incorporate these findings into testable models for the etiology of mitochondrial diseases. (keystonesymposia.org)
  • 10 Moreover, disrupted axonal mitochondrial transport is critical for some diseases. (arvojournals.org)
  • In addition to its role in quality control, deficiencies in PINK/Parkin may also lead to neuroinflammation, thus exacerbating neurodegenerative disease progression. (frontiersin.org)
  • Here we aimed to investigate whether mitochondrial fission induces mtDNA stress and then promotes TAM infiltration and HCC progression. (nature.com)
  • Previous studies have shown that the interaction between HCC cells and tumor microenvironment plays an important role in HCC progression. (nature.com)
  • Results indicate that COUP-TFII may play an oncogenic role in RCC , and COUP-TFII may promote tumor progression through inhibiting BRCA1 . (antikoerper-online.de)
  • They report that mitochondrial fission-fusion is imbalanced in AD subject brains and in transgenic mice expressing human mutant β APP. (alzforum.org)
  • The essential findings are that, in the AD brain, mitochondrial fission seems to be ratcheted up while fusion seems to be ratcheted down. (alzforum.org)
  • Overall, these data are in agreement with other related AD mitochondrial fission-fusion studies, although some divergence from earlier reports is noted. (alzforum.org)
  • Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X . Impaired balance of mitochondrial fission and fusion in Alzheimer's disease . (alzforum.org)
  • The balance between mitochondrial fission and fusion is important in maintaining mitochondrial quality. (diabetesjournals.org)
  • Westermann B (2008) Molecular machinery of mitochondrial fusion and fission. (springer.com)
  • Chan DC (2006) Mitochondrial fusion and fission in mammals. (springer.com)
  • However, mitochondrial fission and fusion are rare, and mitochondrial networks are absent, in adult cardiomyocytes, obviating a need for morphometric mitochondrial remodeling. (ahajournals.org)
  • We further found that mitochondrial dynamics, the balance between mitochondrial fusion and fission, were perturbed by CoCl 2 treatment. (medsci.org)
  • Emerging functions of mammalian mitochondrial fusion and fission. (springer.com)
  • In this article, we investigate β-cell mitochondrial fusion and fission in detail and report alterations in response to various combinations of nutrients. (diabetesjournals.org)
  • We show that Marf (Mitochondrial associated regulatory factor), is required for mitochondrial fusion and transport in long axons. (elifesciences.org)
  • Mitochondrial division and fusion need to be balanced to maintain functional mitochondrial size, structure and distribution within cells. (asbmb.org)
  • assessed whether correcting the imbalance in mitochondrial dynamics with I/R by enhancing fusion would also be protective. (portlandpress.com)
  • Using a rat model, they investigated the efficacy of pharmacological intervention with mitochondrial fusion promoter-M1 (M1) given before ischemia, during ischemia, or at the onset of reperfusion. (portlandpress.com)
  • M1 also prevented a decrease in complex V levels with I/R. However, exactly how M1 stimulates mitochondrial fusion is unclear and other nonfusion-related actions of this phenylhydrazone compound should be considered, such as anti-oxidant actions, preconditioning signaling, or effects on putative mitochondrial connexin 43. (portlandpress.com)
  • The conserved activities of mitochondrial division, fusion, motility and tethering shape and position the dynamic mitochondrial network. (biomedcentral.com)
  • The connectivity of the mitochondrial network is controlled by the antagonistic activities of mitochondrial division and fusion. (biomedcentral.com)
  • examined the role of mitochondrial fission and fusion in mouse cardiomyocytes. (sciencemag.org)
  • Substantial evidence indicates that nuclear receptor signaling is integral to dynamic changes in the cardiac mitochondrial phenotype in response to developmental cues, in response to diverse postnatal physiologic conditions, and in disease states such as heart failure. (jci.org)
  • A subset of cardiac-enriched nuclear receptors serve to match mitochondrial fuel preferences and capacity for ATP production with changing energy demands of the heart. (jci.org)
  • The vast majority of ATP produced in the cardiac myocyte is generated via oxidative phosphorylation (OXPHOS) within a very-high-capacity mitochondrial system. (jci.org)
  • In addition, alterations in nuclear receptor signaling occur with pathologic cardiac growth and remodeling en route to heart failure. (jci.org)
  • 2 ] demonstrated that a lack of mitochondrial dynamism in cardiac myocytes is less deleterious than dynamic imbalance. (portlandpress.com)
  • 1-integrin was found to play a previously uncharacterized role in inflammation-induced vascular permeability, and an antibody against 1-integrin inhibited vascular leakage, improved EC junction integrity and protected from cardiac failure in LPS-induced murine endotoxemia. (helsinki.fi)
  • Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. (uni.lu)
  • Mitochondrial bioenergetics and structural network organization. (springer.com)
  • Connolly NMC, D'Orsi B, Monsefi N, Huber HJ, Prehn JHM (2016) Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions. (plos.org)
  • Mechanistic investigations revealed that the oncogenic effect of MARCH5 was mainly mediated by increased mitochondrial fission and subsequent ROS production in BC cells. (dovepress.com)
  • This study also highlights the crucial role of endothelial 1-integrin in controlling inflammation-induced EC permeability. (helsinki.fi)
  • In this study, we examined how bioenergetic factors affect mitochondrial dynamics/motility in cultured vascular endothelial cells (ECs). (springer.com)
  • Mitochondrial matrix Ca 2+ as an intrinsic signal regulating mitochondrial motility in axons. (springer.com)
  • This indicates that these genes have separate roles in vertebrates, but that these roles are both performed by the single fly gene. (elifesciences.org)
  • Animal models of PD-linked genes also point to axonal impairment as being a critical factor. (jneurosci.org)
  • To further define the role of Phb1 and Gep1 for mitochondrial morphogenesis and Mgm1 processing, we screened for genes whose overexpression promotes growth of cells lacking both genes. (nih.gov)
  • Calcium, ATP, and ROS: a mitochondrial love-hate triangle. (springer.com)
  • As such, mitochondrial networking is thought to be a potential defense mechanism allowing for the buffering of mitochondrial ROS and calcium overload ( 8 , 9 ). (diabetesjournals.org)
  • The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. (plos.org)
  • Right: Electron micrographs showing a mitochondrial constriction site reminiscent of a mitochondrial fission event. (miami.edu)
  • Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. (uni.lu)
  • We found that chemical inhibitors, RNAi silencing, and genetic knockout of TRPM2 channels abolished the ability of high glucose to cause mitochondrial fission in endothelial cells, a cell type that is particularly vulnerable to diabetic stress. (sciencemag.org)
  • Similar to high glucose, increasing ROS in endothelial cells by applying H 2 O 2 induced mitochondrial fission. (sciencemag.org)
  • This manipulation decreased the amplitude and frequency of cytosolic and mitochondrial Ca 2+ signals in isolated cardiomyocytes, without changes in cardiomyocyte contraction. (nih.gov)
  • These results demonstrate that Ryr2 controls mitochondrial Ca 2+ dynamics and plays a specific, critical role in promoting glucose oxidation in cardiomyocytes. (nih.gov)
  • The observed increase in glucose demand occurs on top of mitochondrial energy production and reflects an unregulated increase in the consumption and trapping of glucose beyond the cells' ability to oxidize pyruvate ( 9 , 10 ). (aacrjournals.org)
  • The model further correctly predicted an excitotoxicity-induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. (plos.org)
  • In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult. (plos.org)
  • Increased mitochondrial fission is associated with apoptotic cell death. (alzforum.org)