• Based on this special structure, the fluorescent mitochondrial indicator, nonyl acridine orange (NAO) was introduced in 1982, and was later found to target mitochondria by binding to CL. (wikipedia.org)
  • Several studies were published utilizing NAO both as a quantitative mitochondrial indicator and an indicator of CL content in mitochondria. (wikipedia.org)
  • Finally, a molecule of CDP-DAG is bound to PG to form one molecule of cardiolipin, catalyzed by the mitochondria-localized enzyme cardiolipin synthase (CLS). (wikipedia.org)
  • Hypoxia, due to the lack of oxygen (O2) as the electron recipient, causes inefficient electron transfer through the electron transport chain at the mitochondria leading to accumulation of reactive oxygen species (ROS) which could create irreversible cellular damages. (stanford.edu)
  • Recently, two additional essential functions of cyt c in apoptosis have been discovered that are carried out via its interactions with anionic phospholipids: a mitochondria specific phospholipid, cardiolipin (CL), and plasma membrane phosphatidylserine (PS). (cdc.gov)
  • [5] The eukaryote Monocercomonoides is known to have completely lost its mitochondria, [6] and the multicellular organism Henneguya salminicola is known to have retained mitochondrion-related organelles in association with a complete loss of their mitochondrial genome. (wikipedia.org)
  • Additionally, exacerbated type I IFN responses triggered by mitochondrial DNA (mtDNA), failures in mitophagy, ER-mitochondria communication and mtROS production promote neurodegeneration. (frontiersin.org)
  • The mitochondrial membrane contains the major classes of phospholipids found in all cell membranes, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidic acid (PA), as well as phosphatidylglycerol (PG), the precursor for cardiolipin (CL), which is predominantly located in the mitochondria. (lifestylematrix.com)
  • Mitochondria provide most of the cellular energy via their oxidative phosphorylation (OXPHOS) system, which requires the coordinated expression of genes encoded by both the nuclear (nDNA) and mitochondrial genomes (mtDNA). (biomed.news)
  • Here, we demonstrate that ROS-RET signalling requires increased electron entry and uninterrupted electron flow through the electron transport chain (ETC). We find that in old fruit flies, ROS-RET is abolished when electron flux is decreased and that their mitochondria produce consistently high levels of mtROS. (biomed.news)
  • In line with this notion, mitochondria are highly dynamic organelles that undergo fission and fusion and move into the cell along the microtubules to generate the mitochondrial network [ 6 ]. (hindawi.com)
  • Cardiolipin bicyclic structure Structure of NAO NAO & CL arranged in a highly ordered way The detection, quantification, and localisation of CL species is a valuable tool to investigate mitochondrial dysfunction and the pathophysiological mechanisms underpinning several human disorders. (wikipedia.org)
  • Dox is a mitochondrial toxin, and mitochondrial damage is central to Dox-induced cardiac dysfunction and cell death [ 8 ]. (oncotarget.com)
  • ER stress (ER dysfunction) participates in the development of mitochondrial dysfunction during aging. (bvsalud.org)
  • Mitochondrial dysfunction and the consequent increase in reactive oxygen species also trigger a sequence of events that leads to cell demise. (en-journal.org)
  • The major sources of such oxidative stress generated for the nigral DAergic neurons are thought to be the ROS produced during DA metabolism, mitochondrial dysfunction, and neuroinflammation, as discussed below in more detail. (en-journal.org)
  • One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. (mdpi.com)
  • Nonetheless their association with mitochondrial dysfunction highlights this organelle as an important player during CNS homeostasis and disease. (frontiersin.org)
  • Neuroinflammation and oxidative stress, mitochondrial dysfunction, dysregulation of the expression of histone deacetylases, and aggregation of pathogenic forms of proteins are among the most common and significant pathological features of neurodegenerative diseases. (actanaturae.ru)
  • 1 Many conditions lead to fatigue, but mitochondrial dysfunction is at the core. (lifestylematrix.com)
  • Dysfunction of the mitochondrial electron transport chain (mETC) is a major cause of human mitochondrial diseases. (biorxiv.org)
  • Mitochondrial dysfunction has also been associated with ageing and most of the so-called age-related diseases [ 13 - 17 ]. (hindawi.com)
  • Initially these disorders were named according to symptoms (later the cause was found to be mitochondrial dysfunction and more specifically maternally inherited mitochondrial DNA variations). (medlink.com)
  • Thus, decreasing glycolysis and augmenting mitochondrial function could be beneficial to tackle the disease. (nature.com)
  • Since the (re)discovery of cytochrome c (cyt c) in the early 1920s and subsequent detailed characterization of its structure and function in mitochondrial electron transport, it took over 70 years to realize that cyt c plays a different, not less universal role in programmed cell death, apoptosis, by interacting with several proteins and forming apoptosomes. (cdc.gov)
  • Molecular docking analysis for different enzymes involved in aging (collagenase, elastase and hyaluronidase), antioxidant enzymes (superoxide dismutase, glutathione-s-transferase, glutathione peroxidase and catalase) and mitochondrial enzymes (nicotinamide adenine dinucleotide (NAD)+hydrogen (H) dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and adenosine triphosphate synthase) was carried out for epigallocatechin gallate alone (1), withaferin A alone (2), epigallocatechin gallate and withaferin A in combination (3) and a reference molecule. (ijpsonline.com)
  • Phosphorylation disrupts long-distance electron transport in cytochrome c. (us.es)
  • Review/Rese a: Novel insights into the mechanism of electron transfer in mitochondrial cytochrome c. (us.es)
  • Review/Rese a: Mitochondrial cytochrome c shot towards histone chaperone condensates in the nucleus. (us.es)
  • Countering NADH production, calcium action on the mitochondrial permeability transition pores increases inner membrane permeability thereby reducing proton potential, causing the matrix to swell and ultimately releasing cytochrome c (an initiator of apoptosis). (benbest.com)
  • Electron transport takes place between complexes I-IV and two mobile electron carriers (coenzyme Q and cytochrome c ). (elifesciences.org)
  • Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation. (us.es)
  • The electron transport chain consists of 4 multimeric complexes (I to IV) plus 2 small electron carriers, coenzyme Q10 (or ubiquinone) and cytochrome c . (medlink.com)
  • Complex III or coenzyme Q : cytochrome c - oxidoreductase, sometimes also called the cytochrome bc 1 complex is a complex of the electron transfer pathway . (mitophysiology.org)
  • It catalyzes the reduction of cytochrome c by oxidation of coenzyme Q (CoQ) and the concomitant pumping of 4 protons from the cathodic (negative) mitochondrial matrix to the anodic (positive) intermembrane space. (mitophysiology.org)
  • In several models of lymphocyte apoptosis, two alterations of mitochondrial function precede advanced DNA fragmentation: (1) a reduction of mitochondrial transmembrane potential (delta psi m) and (2) an increase in mitochondrial generation of superoxide anion. (nih.gov)
  • The increase in the heart respiratory chain proteome suggests an increase in mitochondrial oxidative capacity, which could compensate for the energy deficit caused by the inhibition of glycolysis. (nature.com)
  • This phenomenon was not accompanied by an increase in mitochondrial respiratory activity. (elifesciences.org)
  • Vercellino I, Sazanov LA (2022) The assembly, regulation and function of the mitochondrial respiratory chain. (mitophysiology.org)
  • Ganguly U, Bir A, Chakrabarti S (2022) Cytotoxicity of mitochondrial Complex I inhibitor rotenone: a complex interplay of cell death pathways. (mitophysiology.org)
  • Banerjee R, Purhonen J, Kallijärvi J (2022) The mitochondrial coenzyme Q junction and Complex III: biochemistry and pathophysiology. (mitophysiology.org)
  • During electron transport, complexes I, III, and IV pump protons from the mitochondrial matrix to the intermembrane space, generating a proton gradient that provides the protonmotive force exploited by complex V to synthesize ATP. (elifesciences.org)
  • The in-gel activity assay (IGA) is a powerful technique that uses enzymatic activity and compares intensities of detected bands in mitochondrial respiratory chain supercomplexes, and it is applicable to eukaryotic organisms. (biologists.com)
  • In mammalian cells, but also in plant cells, cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane, where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism. (wikipedia.org)
  • Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. (plantbasedacademy.com)
  • Phospholipase D (PLD) in the mitochondrion hydrolyses cardiolipin to phosphatidic acid. (wikipedia.org)
  • The outer mitochondrial membrane contains numerous integral proteins called porins , which contain a relatively large internal channel (about 2-3 nm ) and allow ions and small molecules to move in and out of the mitochondrion. (fact-archive.com)
  • Eth)high cells display a reduced incorporation of the cardiolipin-specific dye nonyl-acridine orange (NAO), showing a structural defect of the cardiolipin-containing inner mitochondrial membrane. (nih.gov)
  • Mammalian mitochondrial respiratory chain (MRC) complexes are able to associate into quaternary structures named supercomplexes (SCs), which normally coexist with non-bound individual complexes. (elifesciences.org)
  • The molecular machinery responsible for energy transformation is the oxidative phosphorylation (OXPHOS) system, which is canonically composed of five multiprotein complexes embedded in the inner mitochondrial membrane. (elifesciences.org)
  • The mETC is comprised of a series of four large inner mitochondrial membrane (IMM) complexes (CI-CIV) that assemble into supercomplexes of defined stoichiometry ( Letts and Sazanov, 2017 ). (biorxiv.org)
  • Reducing equivalents produced in the Krebs cycle and in the beta-oxidation spirals are passed along a series of protein complexes embedded in the inner mitochondrial membrane (the electron transport chain). (medlink.com)
  • They see the biochemical similarities between mitochondrial and bacterial genomes as further evidence for the evolutionary origin of these organelles. (reasons.org)
  • Havird JC, Noe GR, Link L, Torres A, Logan DC, Sloan DB, Chicco AJ (2019) Do angiosperms with highly divergent mitochondrial genomes have altered mitochondrial function? (oroboros.at)
  • But when oxygen is not available in adequate amounts to accept electrons (hydrogen atoms) from NADH, the excess electrons form superoxide from the residual oxygen. (benbest.com)
  • Moreover, silencing of S100A11 stimulated mitochondrial superoxide production, which was decreased by AACOCF 3 , as well as N -acetyl- L -cysteine, which also mimicked the effect of PLA 2 inhibitor on NSCLC chemosensitization upon S100A11 silencing. (oncotarget.com)
  • An interconnected highly integrated system of mitochondrial and cytosolic chaperones and proteases along with the fission/fusion machinery represents the surveillance scaffold of mitostasis. (hindawi.com)
  • Membrane lipid replacement (MLR) is best utilized in the form of an oral phospholipid supplement that emulates the composition of the mitochondrial lipids. (lifestylematrix.com)
  • The inner mitochondrial membrane, in contrast, contains more than 100 different polypeptides , and has a very high protein to phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). (fact-archive.com)
  • Hughes Syndrome/Antiphospholipid syndrome (APS) is a systemic autoimmune, hypercoagulable, thrombo inflammatory, and thrombosis and/or pregnancy complications syndrome caused by the persistent presence of antiphospholipid antibodies (APL) in plasma of patients with vascular thrombosis and/or pregnancy morbidity along with persistent anti-phospholipid antibodies (APLA), including lupus anticoagulant (LA), anti-β2-glycoprotein I (anti-β2GPI) and/or anti-cardiolipin (ACL) antibodies. (endinglines.com)
  • Markers of Parkinson (PD) and Alzheimer (AD) diseases are able to induce innate immune pathways induced by alterations in mitochondrial Ca 2+ homeostasis leading to neuroinflammation. (frontiersin.org)
  • Here, we discuss the importance of these mitochondrial dynamics during neuroinflammation, and how they correlate either with the amelioration or worsening of CNS disease. (frontiersin.org)
  • This view was overturned by the description of mitochondrial diseases. (sciencedaily.com)
  • Despite the impressive accumulation of knowledge of mitochondrial function, the models could not explain the symptoms of these diseases, and researchers were unable to predict who would develop these diseases or how severe they would be, or explain their origin and mechanism. (sciencedaily.com)
  • Recent research has revealed important correlation of mitochondrial dynamics and the pathophysiology of brain diseases, as Alzheimer's. (frontiersin.org)
  • A mutation in the genes regulating any of these functions can result in a variety of mitochondrial diseases . (fact-archive.com)
  • In this review of what is probably the most heterogeneous group of human diseases (the mitochondrial diseases including encephalomyopathies), the author tries to offer the clinician a rational diagnostic framework. (medlink.com)
  • The outer mitochondrial membrane completely encloses the organelle, serving as its outer boundary. (fact-archive.com)
  • The outer mitochondrial membrane, which encloses the entire organelle, is composed of about 50% phospholipids by weight and contains a variety of enzymes involved in such diverse activities such as the oxidation of epinephrine (adrenaline), the degradation of tryptophan , and the elongation of fatty acids . (fact-archive.com)
  • Execution of apoptotic program in cells is accompanied by substantial and early mitochondrial production of reactive oxygen species (ROS). (cdc.gov)
  • Traditionally, MIRI can be due to reactive oxygen and nitrogen species (ROS/RNS) generation, a reduced availability of nitric oxide (NO), Ca 2+ overload, and mitochondrial permeability transition pore (mPTP) opening. (hindawi.com)
  • Mitochondrial reactive oxygen species (mtROS) are cellular messengers essential for cellular homeostasis. (biomed.news)
  • Moreover, the combination of the constituents exhibited better binding for most of the mitochondrial enzymes. (ijpsonline.com)
  • In addition to various enzymes, the mitochondrial matrix also contains ribosomes and several molecules of DNA . (fact-archive.com)
  • Peroxisomes also contain many other metabolic enzymes which sometimes form electron-dense crystalloid cores. (5dok.net)
  • Distinct morphologies of the mitochondrial network support divergent metabolic and regulatory processes that determine cell function and fate1-3. (bvsalud.org)
  • SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. (nature.com)
  • The discovery confirms the model proposed by the team in 2008 to account for observations that could not be explained by the established model of mitochondrial function. (sciencedaily.com)
  • This situation revealed that our knowledge of mitochondrial function was much less complete than had been believed and that our models were inadequate. (sciencedaily.com)
  • By effectively replacing these membrane lipids, mitochondrial function is optimized, and energy production is restored to optimal levels using a safe and cost-effective intervention. (lifestylematrix.com)
  • To identify determinants of mETC function, we screened a genome-wide human CRISPRi library under oxidative metabolic conditions with selective inhibition of mitochondrial Complex III and identified OCIA domain-containing protein 1 (OCIAD1) as a Complex III assembly factor. (biorxiv.org)
  • Havird JC, Shah AA, Chicco AJ (2019) Powerhouses in the cold: mitochondrial function during thermal acclimation in montane mayflies. (oroboros.at)
  • Heim AB, Chung D, Florant GL, Chicco AJ (2017) Tissue-specific seasonal changes in mitochondrial function of a mammalian hibernator. (oroboros.at)
  • The correlation between mitochondrial function and oncogenesis is complex and is not fully understood. (biomed.news)
  • Substrate oxidation-driven electron transfer is coupled to the translocation of protons across the IMM to generate an electrochemical gradient harvested by the ATP synthase (CV) for ATP production. (biorxiv.org)
  • Our understanding of mitochondrial transcription in mammalian cells has largely progressed, but the mechanisms regulating mtDNA gene expression are still poorly understood despite their profound importance for human disease. (biomed.news)
  • Here, we review mechanisms of mitochondrial gene expression with a focus on the recent findings in the field of mammalian mtDNA transcription and disease phenotypes caused by defects in proteins involved in this process. (biomed.news)
  • Blunsom NJ, Gomez-Espinosa E, Ashlin TG, Cockcroft S (2018) Mitochondrial CDP-diacylglycerol synthase activity is due to the peripheral protein, TAMM41 and not due to the integral membrane protein, CDP-diacylglycerol synthase 1. (mitophysiology.org)
  • Chung DJ, Sparagna GC, Chicco AJ, Schulte PM (2018) Patterns of mitochondrial membrane remodeling parallel functional adaptations to thermal stress. (oroboros.at)
  • The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane4,5. (bvsalud.org)
  • The inner mitochondrial membrane is thrown into folds, or cristae , that project inward. (fact-archive.com)
  • The cristae surface houses the machinery needed for aerobic respiration and ATP formation, and their folded form increases that capacity by increasing the surface area of the inner mitochondrial membrane. (fact-archive.com)
  • In prokaryotes such as bacteria, diphosphatidylglycerol synthase catalyses a transfer of the phosphatidyl moiety of one phosphatidylglycerol to the free 3'-hydroxyl group of another, with the elimination of one molecule of glycerol, via the action of an enzyme related to phospholipase D. The enzyme can operate in reverse under some physiological conditions to remove cardiolipin. (wikipedia.org)
  • Despite its fundamental importance, the molecular mechanisms by which OPA1 modulates mitochondrial morphology are unclear. (bvsalud.org)
  • Disturbances in mitochondrial dynamics may influence many cellular and molecular pathways, as calcium-dependent immune activation, transcription factors phosphorylation, cytokine secretion, organelle transference and even cell death. (frontiersin.org)
  • Significant oxidative damage and increased mitochondrial membrane permeability constitute the point-of-no-return of programmed cell death pathways. (lifestylematrix.com)
  • As there are four distinct alkyl chains in cardiolipin, the potential for complexity of this molecule species is enormous. (wikipedia.org)
  • The energy released from the rupture of chemical bonds in food molecules is stored temporarily in the form of high energy electrons in two types of molecule, N and F, whose proportions vary depending on the nutrient source. (sciencedaily.com)
  • An atom or molecule with a net electric charge due to the loss or gain of one or more electrons. (eduhyme.com)
  • Young MP, Schug ZT, Booth DM, Yule DI, Mikoshiba K, Hajnóczky G, Joseph SK (2021) Metabolic adaptation to the chronic loss of Ca 2+ signaling induced by knockout of IP 3 receptors or the mitochondrial Ca 2+ uniporter. (bioblast.at)
  • Sharaf MS, Stevens D, Kamunde C (2017) Mitochondrial transition ROS spike (mTRS) results from coordinated activities of complex I and nicotinamide nucleotide transhydrogenase. (mitophysiology.org)
  • Carballal S, Vitvitsky V, Kumar R, Hanna DA, Libiad M, Gupta A, Jones JW, Banerjee R (2021) Hydrogen sulfide stimulates lipid biogenesis from glutamine that is dependent on the mitochondrial NAD(P)H pool. (bioblast.at)
  • Li Puma LC, Hedges M, Heckman JM, Mathias AB, Engstrom MR, Brown AB, Chicco AJ (2020) Experimental oxygen concentration influences rates of mitochondrial hydrogen peroxide release from cardiac and skeletal muscle preparations. (oroboros.at)
  • Evolutionary biologists view the presence of the diminutive mitochondrial genome as a vestige of this organelle's evolutionary history. (reasons.org)
  • In synthesis, it appears that mitochondrial alterations occur in a significant percentage of circulating T lymphocytes from HIV-1 carriers. (nih.gov)
  • Here we determine the importance of mitochondrial-linked pyrimidine synthesis for the aggressiveness of cancer cells. (biomed.news)
  • The results of this study suggest that inhibition of mitochondrial-linked pyrimidine synthesis in cancer cells results in a more aggressive tumor phenotype. (biomed.news)
  • In addition to being considered a potent antioxidant, melatonin has also been found to play an important role in mitochondrial homeostasis. (eurekaselect.com)
  • [10] Mitochondrial biogenesis is in turn temporally coordinated with these cellular processes. (wikipedia.org)
  • In this review, we discuss the functional cross talk of proteostasis and mitostasis in cellular homeodynamics and the impairment of mitochondrial quality control during ageing, cancer, and neurodegeneration. (hindawi.com)
  • Mitochondrial respiratory chain organization does not seem to be conserved in all organisms. (elifesciences.org)
  • After reminding the reader of the basic concepts of mitochondrial genetics, she offers examples of disorders due to mutations in mitochondrial DNA and mutations in nuclear DNA. (medlink.com)
  • It realized the mitochondrial targeting intracellular imaging to reflect the GGT dynamics in the induction or medicinal treatment of HCC. (bvsalud.org)
  • Notably, the former does not require oxygen, whereas mitochondrial energy production is dependent on oxygen. (nature.com)
  • On the other hand, regulation of mitochondrial dynamics is essential for CNS health maintenance and leading to the induction of IL-10 and reduction of TNF-α secretion, increased cell viability and diminished cell injury in addition to reduced oxidative stress. (frontiersin.org)
  • Categorizing and describing a mitochondrial disorder is complicated in part because there are 3 ways to do so. (medlink.com)
  • Our findings provide a structural framework for understanding how human OPA1 shapes mitochondrial morphology and show us how human disease mutations compromise OPA1 functions. (bvsalud.org)