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PubMed1999

Cytochrome C is released from mitochondria into the cytosol after cerebral anoxia or ischemia.

Mitochondrial dysfunction may underlie both acute and delayed neuronal cell death resulting from cerebral ischemia. Specifically, postischemic release of mitochondrial constituents such as the pro-apoptotic respiratory chain component cytochrome c could contribute acutely to further mitochondrial dysfunction and to promote delayed neuronal death. Experiments reported here tested the hypothesis that ischemia or severe hypoxia results in release of cytochrome c from mitochondria. Cytochrome c was measured spectrophotometrically from either the cytosolic fraction of cortical brain homogenates after global ischemia plus reperfusion, or from brain slices subjected to severe hypoxia plus reoxygenation. Cytochrome c content in cytosol derived from cerebral cortex was increased after ischemia and reperfusion. In intact hippocampal slices, there was a loss of reducible cytochrome c after hypoxia/ reoxygenation, which is consistent with a decrease of this redox carrier in the mitochondrial pool. These results suggest that cytochrome c is lost to the cytosol after cerebral ischemia in a manner that may contribute to postischemic mitochondrial dysfunction and to delayed neuronal death.

Animals↗

PubMed1997

Mitochondrial mutations impair signal transduction in Dictyostelium discoideum slugs.

Subpopulations of mutant mitochondria appear to play important roles in degenerative processes associated with aging and are characteristic of many mitochondrial diseases. We have generated mutants carrying plasmid insertions in the Dictyostelium discoideum mitochondrial genome and have shown that phototaxis and thermotaxis in these mutants is more sensitive than growth and division to the presence of a subpopulation of defective mitochondria. This could result from direct impairment of a mitochondrial role in signal transduction, or indirectly from the effects of energy depletion. Either way, signal transduction may be the first cellular activity to be compromised by the accumulation of defective mitochondria in age-related tissue dysfunction and in mitochondrial disease.

Animals↗

PubMed2005

Building the mitochondrial proteome.

Mitochondria are essential organelles for cellular homeostasis. A variety of pathologies including cancer, myopathies, diabetes, obesity, aging and neurodegenerative diseases are linked to mitochondrial dysfunction. Therefore, mapping the different components of mitochondria is of particular interest to gain further understanding of such diseases. In recent years, proteomics-based approaches have been developed in attempts to determine the complete set of mitochondrial proteins in yeast, plants and mammals. In addition, proteomics-based methods have been applied not only to the analysis of protein function in the organelle, but also to identify biomarkers for diagnosis and therapeutic targets of specific pathologies associated with mitochondria. Altogether, it is becoming clear that proteomics is a powerful tool not only to identify currently unknown components of the mitochondrion, but also to study the different roles of the organelle in cellular homeostasis.

Animals↗

PubMedDate not supplied

Iron metabolism and mitochondrial abnormalities in Friedreich ataxia.

Friedreich ataxia is an autosomal recessive disease causing degeneration in the central and peripheral nervous system, cardiomyopathy, skeletal abnormalities and increased risk of diabetes. It is caused by deficiency of frataxin, a highly conserved nuclear-encoded mitochondrial protein. The genetic mutation found in 98% of Friedreich ataxia chromosomes is the unstable hyperexpansion of a GAA triplet repeat in the first intron of the gene. The expanded GAA repeat, by adopting an abnormal triple helical structure, impairs frataxin transcription. Longer repeats cause a more profound frataxin deficiency and are associated with earlier onset and increased severity of the disease. Yeast cells deficient in the frataxin homologue (Deltayfh1) become unable to carry out oxidative phosphorylation, lose mitochondrial DNA, accumulate iron in mitochondria, show unregulated high expression of high affinity iron uptake, and have an increased sensitivity to oxidative stress. Loss of respiratory competence in Deltayfh1 is iron-dependent. Additional properties of these cells include a deficiency of iron-sulfur cluster containing proteins (ISPs) and impaired iron efflux out of mitochondria. Evidence of oxidative stress, mitochondrial dysfunction, deficiency of multiple ISPs and iron deposits are also found in the human disease and in mouse models. The primary function of frataxin is still unknown, however much recent evidence suggests that it enhances iron-sulfur cluster synthesis and protects iron from free radical-generating reactions. The search for frataxin function stimulated more investigations on the role of mitochondria in cellular iron homeostasis. Their results suggest that these organelles may play a central role in controlling iron homeostasis, which is not surprising considering that they are the major cellular site where this metal is utilized. I propose a model, valid in yeast as well as in higher eukaryotes, in which iron transport into mitochondria is directly coupled to its uptake at the cell membrane and iron transport out of mitochondria depends on adequate iron-sulfur cluster synthesis. Regulatory mechanisms in the cytosol would then sense a post-mitochondrial iron pool. Much circumstantial evidence from genetically manipulated yeast and from human diseases supports this model.

Animals↗

PubMed2000

Ultrastructural localization of cytochrome c in apoptosis demonstrates mitochondrial heterogeneity.

Release of apoptogenic factors into the cytosol including cytochrome c is triggering the execution phase of apoptosis through activation of cytoplasmic effector caspases. How loss of function of the electron transport chain can be reconciled with an adequate energy supply necessary for executing the apoptotic program was studied in granulosa cell (GC) sheets cultured up to 72 h without gonadotrophic support. Cytochrome c was localized ultrastructurally by oxidation of diaminobenzidine tetrahydrochloride both in living and fixed cells. In uncultured GC sheets all cells show staining over their entire mitochondrial population. In 72 h cultured sheets in the absence of FSH pre-apoptotic GC's display two subsets of mitochondria: normal sized stained mitochondria and small orthodox mitochondria without demonstrable cytochrome function. Apoptotic cells contain several mitochondria with preservation of respiratory function besides unstained orthodox mitochondria. The cytochrome c containing mitochondria typically display dilated intracristal spaces, a mitochondrial conformation related to increased ATP production. Cytochrome c release was confirmed by Western blotting. In 72 h cultures supplemented with FSH, GC's displayed staining over their entire mitochondrial population. In cultures lacking FSH, but partially protected from apoptosis through caspase inhibition, the cytochrome c release was not inhibited. Thus in the present studied model dysfunction of only a subset of mitochondria is instrumental to initiate the apoptotic program while a functional electron transport chain is maintained until the degradation phase in a subset of respiring mitochondria.

Animals↗

PubMed1998

Oxidative damage in the senescence-accelerated mouse.

The senescence-accelerated mouse (SAM) exhibited a shortened life span (about 18 months) and early manifestation of various signs of senescence, including changes in physical activity, skin, and spinal curvature. The mechanism of senescence acceleration in SAM is thought to be related to free radical damage. Oxidative phosphorylation was estimated in liver mitochondria from SAMPS and the senescence-resistant subtrain, SAMR1. The respiratory control ratio decreased during aging, and the ATP/O, an index of ATP synthesis, was depressed at 18 months of age in SAMPS. DNP-dependent uncoupled respiration in liver mitochondria was markedly decreased, and active uptake of calcium was markedly dysfunctional with aging. These findings suggest that the functional disorders in mitochondria may be closely related to the shorter life span of SAMPS. White-footed (WF) mice can live at least to 5.5 years, when some animals are still capable of reproducing and their external body condition remains healthy. The mitochondrial functions were examined in the same way as in the SAM experiments. However, no particular finding responsible for their longevity was observed in WF mice at 3 and 12 months old. More comprehensive examinations on more aged WF mice are needed for explanation of their greater longevity.

Aging↗

PubMed1995

[Myocardial hypertrophy and arterial hypertension].

Myocardial hypertrophy in different cardiac diseases is considered to be an adaptive mechanism to the increase of hemodynamic load which might restore to normal radius/wall thickness ratio and consequently to normalize wall stress. However, it has been widely demonstrated that beside the hemodynamic load, other factors contribute to the development of myocardial hypertrophy. It has been shown that in hypertensive patients, functional abnormalities (increased contribution of atrial systole to total diastolic filling, increased isovolumic relaxation period, prolonged diastolic duration, slowed ventricular filling and altered diastolic distensibility) precede the development of myocardial hypertrophy. Thus, in hypertensive patients, sign and symptoms of heart failure could be manifested in absence of myocardial hypertrophy, and might be exclusively due to diastolic dysfunction (with normal systolic function). Systolic function might be involved and compromised late when focal myocardial cell death and fibrosis occur and consequently ¿adequate¿ hypertrophy is shifted to ¿inadequate¿. This evolution is accompanied by morphological and functional changes of the myocardium similar to those encountered in dilated cardiomyopathy. Impairment of systolic function in ¿inadequate¿ hypertrophy is also due to structural changes; altered ratio between sarcomers and mitochondria, increased intercapillary distance, sarcoplasmatic reticulum dysfunction, increase of collagene component with a consequent increment of wall rigidity, hypertrophy of arterial tunica media, which alters coronary flow and coronary reserve. The progression of these morpho-functional abnormalities is a very slow process, in which adaptive mechanism mediated by several enzymes and contractile protein, contribute to maintain myocardial viability. However, over the long course, disseminated focal myocardial cell necrosis and fibrosis, which is an evolving process, is considered to be the main responsible factor for the irreversible myocardial damage and systolic dysfunction in advanced myocardial inadequate hypertrophy.

Cardiomegaly↗

PubMed2007

The role of mitochondrial function in the oocyte and embryo.

Mitochondria have long been known to be the powerhouses of the cell but they also contribute to redox and Ca2+ homeostasis, provide intermediary metabolites and store proapoptotic factors. Mitochondria have a unique behavior during development. They are maternally transmitted with little (if any) paternal contribution, and they originate from a restricted founder population, which is amplified during oogenesis. Then, having established the full complement of mitochondria in the fully grown oocyte, there is no further increase of the mitochondrial population during early development. The localization of mitochondria in the egg during maturation and their segregation to blastomeres in the cleaving embryo are strictly regulated. Gradients in the distribution of mitochondria present in the egg have the potential to give rise to blastomeres receiving different numbers of mitochondria. Such maternally inherited differences in mitochondrial distribution are thought to play roles in defining the long-term viability of the blastomere in some cases and embryonic axes and patterning in others. Mitochondria may also regulate development by a number of other means, including modulating Ca2+ signaling, and the production of ATP, reactive oxygen species, and intermediary metabolites. If the participation of mitochondria in the regulation of sperm-triggered Ca2+ oscillations is now well established, the role of other properties of mitochondrial function during development remain largely unexplored probably due to the difficulty of accessing the mitochondrial compartment in an embryo. Maintaining a functional complement of maternally derived mitochondria is vital for the early embryo. Mitochondrial dysfunction may not only compromise developmental processes but also trigger apoptosis in the embryo. This dual role for mitochondria (to maintain life or to commit to cell death) may well represent a quality control system in the early embryo that will determine whether the embryo proceeds further into development or is quickly eliminated.

Adenosine Triphosphate↗

PubMed2000

Granzyme B induces BID-mediated cytochrome c release and mitochondrial permeability transition.

Many cell death pathways converge at the mitochondria to induce release of apoptogenic proteins and permeability transition, resulting in the activation of effector caspases responsible for the biochemical and morphological alterations of apoptosis. The death receptor pathway has been described as a triphasic process initiated by the activation of apical caspases, a mitochondrial phase, and then the final phase of effector caspase activation. Granzyme B (GrB) activates apical and effector caspases as well as promotes cytochrome c (cyt c) release and loss of mitochondrial membrane potential. We investigated how GrB affects mitochondria utilizing an in vitro cell-free system and determined that cyt c release and permeability transition are initiated by distinct mechanisms. The cleavage of cytosolic BID by GrB results in truncated BID, initiating mitochondrial cyt c release. BID is the sole cytosolic protein responsible for this phenomenon in vitro, yet caspases were found to participate in cyt c release in some cells. On the other hand, GrB acts directly on mitochondria in the absence of cytosolic S100 proteins to open the permeability transition pore and to disrupt the proton electrochemical gradient. We suggest that GrB acts by two distinct mechanisms on mitochondria that ultimately lead to mitochondrial dysfunction and cellular demise.

Animals↗

PubMed2005

Zidovudine-induced diaphragmatic contractile dysfunction: impact of an antioxidant diet.

OBJECTIVE: Zidovudine (AZT) is a primary drug therapy used to treat HIV-infected individuals. While AZT inhibits replication of HIV, it also induces a drug-specific myopathy resulting in altered muscle mitochondria, increased oxidative stress and muscle contractile dysfunction. The purpose of this study was to assess the impact of an antioxidant diet (high in vitamins C and E) on AZT-mediated diaphragmatic contractile dysfunction in rodents. METHODOLOGY: Adult, Sprague-Dawley rats were assigned to feeding groups: control (CON, n = 9), AZT-treatment (AZT, n = 8), antioxidant diet only (Anti-Ox, n = 6), and AZT + antioxidant diet (AZT + Anti, n = 9). Two costal diaphragm strips were removed from each animal (under surgical anaesthesia) and evaluated for force-frequency relationship, maximal specific tension, and fatigue resistance using an in vitro preparation. RESULTS: Results indicate significant reductions in normalized force production (20-200 Hz), including maximal specific tension, between AZT animals and all other groups. While AZT reduced diaphragm contractility, the addition of an antioxidant diet eliminated this decrease. CONCLUSION: These data suggest that an increase in oxidative stress mediated by AZT may contribute to AZT-induced muscle contractile dysfunction, and that antioxidant vitamin supplementation may help ameliorate this effect.

Animals↗

PubMed2005

Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity.

Apolipoprotein (apo) E4, a 299-aa protein and a major risk factor for Alzheimer's disease, can be cleaved to generate C-terminal-truncated fragments that cause neurotoxicity in vitro and neurodegeneration and behavioral deficits in transgenic mice. To investigate this neurotoxicity, we expressed apoE4 with C- or N-terminal truncations or mutations in transfected Neuro-2a cells. ApoE4 (1-272) was neurotoxic, but full-length apoE4(1-299) and apoE4(1-240) were not, suggesting that the lipid-binding region (amino acids 241-272) mediates the neurotoxicity and that amino acids 273-299 are protective. A quadruple mutation in the lipid-binding region (I250A, F257A, W264R, and V269A) abolished the neurotoxicity of apoE4(1-272), and single mutations in the region of amino acids 273-299 (L279Q, K282A, or Q284A) made full-length apoE4 neurotoxic. Immunofluorescence staining showed that apoE4(1-272) formed filamentous inclusions containing phosphorylated tau in some cells and interacted with mitochondria in others, leading to mitochondrial dysfunction as determined by MitoTracker staining and flow cytometry. ApoE4(241-272) did not cause mitochondrial dysfunction or neurotoxicity, suggesting that the lipid-binding region alone is insufficient for neurotoxicity. Truncation of N-terminal sequences (amino acids 1-170) containing the receptor-binding region (amino acids 135-150) and triple mutations within that region (R142A, K146A, and R147A) abolished the mitochondrial interaction and neurotoxicity of apoE4(1-272). Further analysis showed that the receptor-binding region is required for escape from the secretory pathway and that the lipid-binding region mediates mitochondrial interaction. Thus, the lipid- and receptor-binding regions in apoE4 fragments act together to cause mitochondrial dysfunction and neurotoxicity, which may be important in Alzheimer's disease pathogenesis.

Alzheimer Disease↗

PubMed1988

Role of arachidonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia.

The aim of the present investigation was to evaluate the possible role of arachidonic acid and other free fatty acids in ischemia-induced mitochondrial dysfunction. Respiratory activities were measured in mitochondria isolated from rat brains subjected to 15-30 min of decapitation ischemia. Addition of bovine serum albumin (BSA) to the mitochondria, isolated in BSA-free media, abolished an ischemia-induced increase in substrate-stimulated (state 4) respiration but only partly reversed a marked inhibition of substrate-, phosphate-, and ADP-stimulated (state 3) respiration caused by the ischemia. Individual free fatty acids were measured in aliquots of the same mitochondrial preparations before and after treatment with BSA. There was a significant increase in arachidonic (20:4), stearic (18:0), palmitic (16:0), and docosahexaenoic (22:6) acid during ischemia. BSA treatment removed all 20:4 and reduced the amount of 18:0 and 16:0, but had no significant effect on 22:6. The main conclusions were 1) that 20:4, 18:0, and 16.0 were responsible for the partial uncoupling (increase in state 4 respiration) of mitochondrial respiration during ischemia, 2) that the inhibition of state 3 respiration caused by ischemia could only partly be attributed to an effect of FFAs, and 3) that the ischemia-induced mitochondrial dysfunction was caused by a combination of factors including 20:4.

Animals↗

PubMed1992

Studies on the hepatotoxicity induced by bis (tributyltin) oxide.

The toxic effects of bis (tributyltin) oxide (TBTO) on the rat liver were studied with an electron microscope and the accumulation sites of tin were determined with an X-ray microanalyzer. The activities of serum enzymes and the concentration of serum bilirubin were also analyzed. Male Wistar rats received an intramuscular injection of 0.5 ml/kg of TBTO. Marked swelling of the mitochondria appeared in the hepatocytes 4 h after injection of TBTO. Cytoplasmic vacuoles, which contained degenerated mitochondria, gradually increased in number in these hepatocytes. This in turn may have caused a decrease in the volume of hepatic cell cords and an enlargement of sinusoids in the entire hepatic lobule. However, fine structures of intrahepatic bile ducts were not altered. By X-ray microanalysis, tin peaks were preferentially obtained from swollen mitochondria of the hepatocytes. By polarographic analysis of the respiratory responses of mitochondria, it was demonstrated that rates of state 4 respiration and respiratory control ratio were significantly disturbed in TBTO-treated rats in comparison with those of controls. The activities of AST (aspartate aminotransferase) and ALT (alanine aminotransferase) were significantly increased after TBTO treatment, but those of ALP (alkaline phosphatase), LAP (leucine aminopeptidase) and total bilirubin were not changed. These results indicated that parenterally administered TBTO accumulated in the liver cell mitochondria and disturbed oxidative phosphorylation. Mitochondrial dysfunction might induce severe damage of the hepatocytes. Four days after injection of TBTO, hepatic structures and chemical indices were almost restored by the regeneration of hepatocytes.

Alanine Transaminase↗

PubMed1979

Evidence for Leydig cell dysfunction in rats with seminiferous tubule damage.

To study the effects of seminiferous tubule damage on Leydig cell function and morphology, rats were treated by fetal irradiation (to induce Sertoli cell-only syndrome, SCO), 3 months administration of hydroxyurea (HU), or chronic feeding of a vitamin A-deficient diet (VAD). Leydig cell function was assessed by the measurement of serum LH and testosterone and the response of serum testosterone to hCG stimulation, while morphology was studied by electron microscopy after perfusion fixation. Serum LH was significantly elevated in each experimental group, while basal serum testosterone was significantly lower only in SCO rats. In all treatment groups, the serum testosterone response to hCG was significantly decreased when measureed as the area under the response curve. Despite a decreased response to hCG, the Leydig cells were larger than normal and showed striking increases in quantities of smooth endoplasmic reticulum, mitochondria and Golgi complex. Leydig cell dysfunction has been demonstrated in animals with varying degrees of seminiferous tubule damage, but paradoxically the cytological features of the Leydig cells were indicative of hypertrophy.

Animals↗

PubMed2005

Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid beta-oxidation and glucose.

Mitochondrial cytopathy has been associated with modifications of lipid metabolism in various situations, such as the acquisition of an abnormal adipocyte phenotype observed in multiple symmetrical lipomatosis or triglyceride (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged red fibers syndrome. However, the molecular signaling leading to fat metabolism dysregulation in cells with impaired mitochondrial activity is still poorly understood. Here, we found that preadipocytes incubated with inhibitors of mitochondrial respiration such as antimycin A (AA) accumulate TG vesicles but do not acquire specific markers of adipocytes. Although the uptake of TG precursors is not stimulated in 3T3-L1 cells with impaired mitochondrial activity, we found a strong stimulation of glucose uptake in AA-treated cells mediated by calcium and phosphatidylinositol 3-kinase/Akt1/glycogen synthase kinase 3beta, a pathway known to trigger the translocation of glucose transporter 4 to the plasma membrane in response to insulin. TG accumulation in AA-treated cells is mediated by a reduced peroxisome proliferator-activated receptor gamma activity that downregulates muscle carnitine palmitoyl transferase-1 expression and fatty acid beta-oxidation, and by a direct conversion of glucose into TGs accompanied by the activation of carbohydrate-responsive element binding protein, a lipogenic transcription factor. Taken together, these results could explain how mitochondrial impairment leads to the multivesicular phenotype found in some mitochondria-originating diseases associated with a dysfunction in fat metabolism.

3T3-L1 Cells↗

PubMed2004

Indomethacin-induced renal damage: role of oxygen free radicals.

Nonsteroidal anti-inflammatory drugs are used extensively in clinical medicine. In spite of their therapeutic utility, however, they are known to cause significant gastrointestinal and renal toxicities, circumstances that limit their use. The side effects produced in these organs have been attributed mainly to the inhibitory effect of these drugs on the activity of cyclooxygenase, a key enzyme in prostaglandin synthesis. In addition to this, in the small intestine it is known that reactive oxygen species also contribute to the enteropathy seen in response to these drugs. In the kidney, however, there is little information whether other mechanisms contribute to the renal toxicity. This study was designed to look at the possible biochemical mechanisms involved in indomethacin-induced renal damage. Rats fasted overnight were dosed with indomethacin (20 mg/kg) by gavage and sacrificed 24 hr later. Histology of the kidney showed abnormalities in the mitochondria in the proximal tubules. Evidence of oxidative stress was found in the kidney associated with mitochondrial dysfunction and neutrophil infiltration. The lipid composition in the mitochondria was also altered. Such effects were abolished by the prior administration of arginine, a donor of nitric oxide. This study, thus, suggests that one of the mechanisms by which nonsteroidal anti-inflammatory drugs induce renal damage is through oxygen free radicals possibly generated by activated neutrophils and mitochondrial dysfunction.

Animals↗

PubMed2003

Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis.

BACKGROUND: Propofol is an intravenous anesthetic agent that may impair host defense system. The aim of this study was to evaluate the effects of propofol on macrophage functions and its possible mechanism. METHODS: Mouse macrophage-like Raw 264.7 cells were exposed to propofol, at 3, 30 (a clinically relevant concentration), and 300 microm. Cell viability, lactate dehydrogenase, and cell cycle were analyzed to determine the cellular toxicity of propofol to macrophages. After administration of propofol, chemotactic, phagocytic, and oxidative ability and interferon-gamma mRNA production were carried out to validate the potential effects of propofol on macrophage functions. Mitochondrial membrane potential and cellular adenosine triphosphate levels were also analyzed to evaluate the role of mitochondria in propofol-induced macrophage dysfunction. RESULTS: Exposure of macrophages to 3 and 30 microm propofol did not affect cell viability. When the administered concentration reached 300 microm, propofol would increase lactate dehydrogenase release, cause arrest of cell cycle in G1/S phase, and lead to cell death. In the 1-h-treated macrophages, propofol significantly reduced macrophage functions of chemotactic and oxidative ability in a concentration-dependent manner. However, the suppressive effects were partially or completely reversed after 6 and 24 h. Propofol could reduce phagocytic activities of macrophages in concentration- and time-dependent manners. Exposure of macrophages to lipopolysaccharide induced the mRNA of interferon-gamma, but the induction was significantly blocked by propofol. Propofol concentration-dependently decreased the membrane potential of macrophage mitochondria, but the effects were descended with time. The levels of cellular adenosine triphosphate in macrophages were also reduced by propofol. CONCLUSIONS: A clinically relevant concentration of propofol can suppress macrophage functions, possibly through inhibiting their mitochondrial membrane potential and adenosine triphosphate synthesis instead of direct cellular toxicity.

Actins↗

PubMed2005

MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction.

To investigate the regulatory system in mitochondrial biogenesis involving crosstalk between the mitochondria and nucleus, we found a factor named MIDAS (mitochondrial DNA absence sensitive factor) whose expression was enhanced by the absence of mitochondrial DNA (mtDNA). In patients with mitochondrial diseases, MIDAS expression was increased only in dysfunctional muscle fibers. A majority of MIDAS localized to mitochondria with a small fraction in the Golgi apparatus in HeLa cells. To investigate the function of MIDAS, we stably transfected HeLa cells with an expression vector carrying MIDAS cDNA or siRNA. Cells expressing the MIDAS protein and the siRNA constitutively showed an increase and decrease in the total mass of mitochondria, respectively, accompanying the regulation of a mitochondria-specific phospholipid, cardiolipin. In contrast, amounts of the mitochondrial DNA, RNA and proteins did not depend upon MIDAS. Thus, MIDAS is involved in the regulation of mitochondrial lipids, leading to increases of total mitochondrial mass in response to mitochondrial dysfunction.

Cardiolipins↗