PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Mitochondrial function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1997

The conservation of mitochondrial function by ischaemia--the ischaemia paradox.

The aim of this study was to compare oxidative phosphorylation of rat heart mitochondria, isolated: (i) immediately after excision of the heart; (ii) after 60 min of low flow normoxic perfusion; (iii) after 60 min of high flow normoxic perfusion;: (iv) after 30 min of no-flow ischaemia and (v) after 30 min ischaemia followed by 20 min reperfusion. The results, using a retrogradely perfused rat hart as a model, show that mitochondrial oxidative phosphorylation after 30 min of no-flow ischaemia showed no difference from oxidative phosphorylation measured on mitochondria isolated directly after excision of the heart. However, after 30 min no-flow ischaemia followed by 20 min of reperfusion, oxidative phosphorylation deteriorated in comparison with oxidative phosphorylation after 30 min of ischaemia only. Furthermore, oxidative phosphorylation after 60 min of non-ischaemic high flow perfusion (thus high coronary flow), compared better with oxidative phosphorylation after ischaemia-reperfusion than with oxidative phosphorylation after ischaemia alone.

Animals↗
PubMed1997

The hepatotoxicity of rhein involves impairment of mitochondrial functions.

Metabolism of rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) in primary cultures of rat hepatocytes caused production of oxygen-derived free radicals by redox cycling; this was shown as an increased rate of superoxide-dismutasesensitive NAD(P)H oxidation and NAD(P)H-cytochrome c reduction. Furthermore, rhein caused a depletion of intracellular reduced glutathione and an immediate, almost 10-fold increase in intracellular free Ca2+. Exposure to rhein also induced the following: a decrease in the mitochondrial membrane potential, as analyzed by uptake of rhodamine 123 (Rh 123); initiation of lipid peroxidation, measured as accumulation of malondialdehyde and 4-hydroxyalkenals; and cell death (LD50 = 20 microM). Pretreatment of cell cultures with dithiothreitol (DTT), nifedipin or N',N'-diphenyl-p-phenylenediamine (DPPD) increased the intracellular free Ca2+ concentration 5-fold but inhibited rhein-induced cytotoxicity. Moreover, addition of these protecting substances maintained the level of ATP and glutathione (GSH) and prevented accumulation of lipid peroxidation products. Depletion of intracellular glutathione by pretreatment with buthionine sulfoximine (BSO), or inhibition of glutathione reductase with 1,3-bis-2-chloroethyl-1-nitrosourea (BCNU) decreased cell viability (LD50 = 2.5 microM). On the other hand, increasing GSH by pretreatment with L-2-oxothiazolidine-4-carboxylic acid (OTC) did not provide complete protection. In summary, rhein undergoes redox cycling that gives rise to oxygen metabolites that affect the mitochondrial membranes (recorded as a decreased membrane potential) and after the plasma membrane (i.e. induced the formation of surface blebs). Mitochondrial malfunction also causes changes in Ca2+ homeostasis and depletion of ATP, which eventually lead to cell death.

Adenosine Triphosphate↗
PubMed2003

Islet beta-cell apoptosis triggered in vivo by interleukin-1beta is not related to the inducible nitric oxide synthase pathway: evidence for mitochondrial function impairment and lipoperoxidation.

IL-1beta is recognized as an effector cytokine contributing to islet beta-cell destruction during diabetes. We have previously shown in vitro that IL-1beta induces nitric oxide (NO) and beta-cell damage. Here, we show that IL-1beta administration in vivo to Wistar rats transiently increases manganese superoxide dismutase activity, whereas inducible NO synthase is not detected, and the levels of nitrate+nitrate do not change. Moreover, a significant decrease of mitochondrial aconitase, leading to a rise of hydroperoxides, and islet beta-cell apoptosis, involving caspase-3 and -8, is observed. Analysis of adhesion molecules in beta-cells showed that intercellular adhesion molecule-1 is highly expressed 48 h after IL-1beta administration and that this is concomitant to the fall of manganese superoxide dismutase activity. Thus, IL-1beta exerts a proapoptotic effect in vivo through mitochondrial enzyme alteration, which is not related to the inducible NO synthase pathway, and dysregulates the immune system through the up-regulation of adhesion molecules.

Aconitate Hydratase↗
PubMedDate not supplied

[The effect of mexamine on liver mitochondrial function in rats in vivo and in vitro from the aspect of the mechanisms of the pharmacological and radioprotective action of the protector].

The polarographic study of the functional status (FS) of rat liver mitochondria subjected to the effect of mexamine in vivo and in vitro and the hypoxic hypoxia in vivo has revealed various FS changes displaying disconnecting and rotenone-like effects and posthypoxic activation. With a mexamine dose of 50 mg/kg in vivo the direct effect of the protector contributes considerably to the mitochondrial FS. Within a wide range of mexamine doses no relationship was found between the pattern of the mitochondrial FS change in the liver and the protective effect with respect to bone marrow.

5-Methoxytryptamine↗
PubMed1993

Pyrophosphate metabolism in the perfused heart and isolated heart mitochondria and its role in regulation of mitochondrial function by calcium.

1. Langendorff-perfused rat hearts were treated, either alone or in combination, with acetate, adrenaline or supraphysiological [Ca2+] to mimic increased workload. No significant increases in the PPi content of the freeze-clamped tissue were observed. 2. In contrast with liver mitochondria, isolated rat heart mitochondria incubated at a free [Mg2+] of 1.5 mM showed little or no increase in matrix PPi content or volume in the presence of 0.75 microM Ca2+; neither did 5 mM acetate cause heart mitochondrial PPi to increase. 3. At 0.1 mM Mg2+ some increase in matrix PPi content of heart mitochondria was observed, and increases in liver mitochondria were significantly greater. 4. Substantial increases in heart mitochondrial-matrix PPi content were observed at 1.5 mM Mg2+ when [Ca2+] > 1 microM, especially in the presence of acetate, or at 0.75 microM Ca2+ in the presence of bongkrekic acid to inhibit the adenine nucleotide translocase. 5. Total pyrophosphatase activity was similar in heart and liver mitochondrial matrix extract and toluene-permeabilized mitochondria. 6. These data suggest that under physiological conditions Ca2+ does not regulate heart mitochondrial [PPi], because higher matrix [Mg2+] overcomes the inhibition of pyrophosphatase by Ca2+, and also significant loss of PPi from the matrix on the adenine nucleotide translocase may occur. 7. It is concluded that, in contrast with the situation in liver [Halestrap (1989) Biochim. Biophys. Acta 973, 355-382], Ca(2+)-induced PPi-mediated increases in mitochondrial volume are unlikely to play a physiological role in the heart. 8. The substantial swelling of liver and kidney mitochondria caused by addition of supraphysiological [Ca2+] (20 nmol/mg of protein) was associated with significant increases in PPi content, but was not observed in heart mitochondria. 9. This substantiates the role that we have proposed for PPi in the opening of a non-specific pore by Ca2+ overload of mitochondria [Halestrap and Davidson (1990) Biochem. J. 268, 153-160].

Animals↗
PubMed1997

Oxygen dependence of mitochondrial function measured by high-resolution respirometry in long-term hypoxic rats.

Respiration and oxidative phosphorylation were investigated in tightly coupled mitochondria isolated from liver and heart of rats submitted to a simulated altitude of 4,400 m for 14-15 mo and their corresponding controls at sea level. High-resolution respirometry was utilized to determine the apparent Michaelis-Menten constant for ADP and O2 (K(m)-ADP and K(m)-O2, respectively), the latter under active and resting states of mitochondrial respiration. The K(m)-O2 in mitochondria isolated from normoxic rats was higher for active (state 3) than for resting (state 4) respiration; the values decreased from 1.5 and 1.7 to 0.25 and 0.30 microM in heart and liver mitochondria, respectively. The K(m)-O2 values found in the active state suggest a role for the normally occurring intracellular PO2 range reported in the literature in the regulation of cellular respiration. No changes were found in the ADP or O2 dependence of respiration in the mitochondria isolated from long-term acclimatized rats compared with their controls, indicating that the intrinsic properties and the efficiency of mitochondria do not change as a consequence of adaptation to hypoxia.

Adenosine Diphosphate↗
PubMed1998

mtDNA depletion and impairment of mitochondrial function in a case of a multisystem disorder including severe myopathy.

The ratio of mtDNA and a nuclear reference gene was estimated by Southern blotting in the skeletal muscle DNA of a 3-year-old girl who suffered from congenital brain damage, focal epilepsy, hepatomegaly, malabsorption syndrome and severe myopathy. The signal ratio of mtDNA versus 18S rDNA was 22% of the mean value obtained from controls. No major deletions or insertions were found and the MERRF, MELAS and NARP mutations were ruled out. Mitochondrial DNA-encoded enzyme activities and mitochondrial respiration were reduced. The analysis of the NAD(P)H and flavoprotein redox states of intact fibres revealed the presence of mitochondrial dysfunction. In tissue sections a moderate elevation of type I and type II fibre diameter variation was detected, aberrant NADH- and succinate dehydrogenase staining and some ragged red fibres. This suggested that a mitochondrial disorder caused by a decrease in the amount of intact wild-type mtDNA was responsible for the severe myopathy.

Abnormalities, Multiple↗
PubMed2007

Impairment of mitochondrial function by particulate matter (PM) and their toxic components: implications for PM-induced cardiovascular and lung disease.

Increasing evidence suggests that reactive oxygen species (ROS) and oxidative stress are involved in PM-mediated lung and cardiovascular injury. The physical characteristics and the chemical composition of particulate matter (PM) play a key role in ROS generation in vitro and in vivo. The mitochondria are major subcellular targets for PM as well as a source of ROS production. ROS production is due to interference in mitochondrial electron transfer and PT pore opening by pro-oxidative PM components. Another possible mechanism is direct physical targeting by ambient ultrafine particles that lodge in and destroy mitochondrial structure. An understanding of the mitochondrial effects of PM is key in understanding the mechanisms of PM-induced adverse health effects.

Air Pollutants↗
PubMed2004

Increased expression of heat shock proteins in rat brain during aging: relationship with mitochondrial function and glutathione redox state.

It is generally recognized that lipid peroxides play an important role in the pathogenesis of several diseases and that sulfhydryl groups are critically involved in cellular defense against endogenous or exogenous oxidants. Recent evidence indicates that lipid peroxides directly participate in induction of cytoprotective proteins, such as heat shock proteins (Hsps), which play a central role in the cellular mechanisms of stress tolerance. Oxidative damage plays a crucial role in the brain aging process and induction of Hsps is critically utilized by brain cells in the repair process following various pathogenic insults. In the present study, we investigated, in rats 6, 12, and 28 months old, the role of heat shock expression on aging-induced changes in mitochondrial and antioxidant redox status. In the brain expression of Hsp72 and Hsc70 increased with age up to 28 months; at this age the maximum induction was observed in the hippocampus and substantia nigra followed by cerebellum, cortex, septum and striatum. Hsps induction was associated with significant changes in glutathione (GSH) redox state and HNE levels. Interestingly, a significant positive correlation between decrease in GSH and increase in Hsp72 was observed in all brain regions examined during aging. Analysis of mitochondrial complexes showed a progressive decrease of Complex I activity and mRNA expression in the hippocampus and a significant decrease of Complex I and IV activities in the substantia nigra and septum. Our results sustain a role for GSH redox state in Hsp expression. Increase of Hsp expression promotes the functional recovery of oxidatively damaged proteins and protects cells from progressive age-related cell damage. Conceivably, heat shock signal pathway by increasing cellular stress resistance may represent a crucial mechanism of defence against free radical-induced damage occurring in aging brain and in neurodegenerative disorders.

Aging↗
PubMed1988

Mitochondrial function in rats is affected by modification of membrane phospholipids with dietary sardine oil.

Phospholipids of heart and liver of rats fed a diet containing sardine oil had more omega 3 polyunsaturated fatty acids and less omega 6 polyunsaturated fatty acids than those of rats fed corn oil, whereas there was little difference in the fatty acid composition of brain phospholipids. The mass of phospholipid classes in rat heart mitochondria was not changed, but their fatty acid compositions were altered. Modification of the fatty acid compositions of mitochondrial phosphatidylcholine and phosphatidylethanolamine reached a plateau after 10 d of feeding, but that of cardiolipin continued for 30 d. The O2 consumption rate of rat heart mitochondria decreased as the fatty acid composition of the phospholipids changed. This may be due to the reduction of the activity of cytochrome c oxidase, which requires cardiolipin for its activity. However, F1F0-ATPase, which also requires cardiolipin, was activated under the same conditions.

Animals↗
PubMed1992

The preservation of mitochondrial functions in extracellular environments.

Mitochondria are labile objects when isolated from mammalian organs and may undergo rapid changes (aging) in vitro. This work attempts to examine conditions which retard such changes. Isolated rat heart mitochondria were incubated for 180 min in the presence of various substances whose properties might influence the aging process as expressed by changes in oxygen consumption rates. It was found that retardation was greatest with substances which potentially influence reactions involving fatty acids. This effect is discussed in terms of various mechanisms of mitochondrial aging.

Aging↗
PubMed1997

Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin.

Friedreich's ataxia is due to loss of function mutations in the gene encoding frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization analyses revealed that mouse frataxin expression correlates well with the main site of neurodegeneration, but the expression pattern is broader than expected from the pathology of the disease. Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate, including liver, kidney, brown fat and heart. We found that mouse and yeast frataxin homologues contain a potential mitochondrial targeting sequence in their N-terminal domains and that disruption of the yeast gene results in mitochondrial dysfunction. Finally, tagging experiments demonstrate that human frataxin co-localizes with a mitochondrial protein. Friedreich's ataxia is therefore a mitochondrial disease caused by a mutation in the nuclear genome.

Amino Acid Sequence↗
PubMed2002

Type I interferon gene transfer sensitizes melanoma cells to apoptosis via a target activity on mitochondrial function.

Our previous article reported that retroviral transduction of human type I consensus interferon-coding sequence into two human melanoma cells increased their susceptibility to cisplatin-induced apoptosis. Importantly, primary melanoma cells were significantly more sensitive to cisplatin-induced apoptosis with respect to metastatic melanoma cells. The aim of this study was to elucidate the subcellular mechanisms involved in this interferon-induced apoptotic proneness. Our results indicate that 1) cisplatin-induced apoptosis can be referred to as the type II apoptosis, ie, to the mitochondrially driven cascade; 2) treatment of interferon-producing melanoma cells with other type II apoptotic stimuli, such as radiation or staurosporine, also resulted in massive apoptosis, whereas type I stimuli, ie, anti-Fas, were ineffective; 3) interferon sensitization involved the caspase cascade in primary melanoma cells and the alternative pathway represented by cathepsin-mediated apoptosis in metastatic melanoma cells; 4) interferon production sensitizes cells to apoptosis by inducing, as the earliest event, mitochondrial membrane hyperpolarization. These results suggest that constitutive production of type I interferon by melanoma cells can act as an intracellular booster capable of increasing cell proneness to apoptosis by specifically modifying mitochondrial homeostasis and independently from the apoptotic cascade involved.

Antineoplastic Agents↗
PubMedDate not supplied

Effect of exhaustive exercise on liver mitochondrial function in the rat.

The oxidative and phosphorylative function of rat liver mitochondria after exhaustive exercise was investigated. The stimulation of state 4 respiration (without ADP) with NADH and FADH2 dependent substrates was demonstrated. The reduction in RCR ratio (the rate of oxidation in state 3/the rate of oxidation in state 4) and enhanced activity of oligomycin sensitive ATP-ase was also found. The results suggest an inhibition of liver mitochondrial phosphorylative activity in rats exercised till exhaustion.

Adenosine Triphosphatases↗
PubMed2004

Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function.

Cannabinoids and endocannabinoids negatively influence sperm functions. These substances have been demonstrated in many mammalian tissues, including male and female reproductive tracts, and previous studies have shown the presence of functional receptors for cannabinoids in human sperm. The present study, by means of RT-PCR and Western blot techniques, demonstrates that human sperm express the CB(1), but not CB(2), cannabinoid receptor (CB-R) subtype located in the head and middle piece of the sperm. The activation of this receptor by anandamide reduces sperm motility and inhibits capacitation-induced acrosome reaction. Activation of the CB(1)-R did not induce any variation in sperm intracellular calcium concentrations, but produced a rapid plasma membrane hyperpolarization that was reduced by the K(+) channel blocker tetraethylammonium. The effects of anandamide on human sperm motility were dependent on the reduction of sperm mitochondrial activity as determined by rhodamine 123 fluorescence. The specificity of anandamide effects in human sperm were confirmed by the effects of the CB(1)-R antagonist SR141716. These findings provide additional evidence that human sperm express functional CB(1)-R, the activation of which negatively influences important sperm functions, and suggest a possible role for the cannabinoid system in the pathogenesis of some forms of male infertility.

Acrosome Reaction↗
PubMed2003

Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells.

Alzheimer's amyloid precursor protein 695 (APP) is a plasma membrane protein, which is known to be the source of the toxic amyloid beta (Abeta) peptide associated with the pathogenesis of Alzheimer's disease (AD). Here we demonstrate that by virtue of its chimeric NH2-terminal signal, APP is also targeted to mitochondria of cortical neuronal cells and select regions of the brain of a transgenic mouse model for AD. The positively charged residues at 40, 44, and 51 of APP are critical components of the mitochondrial-targeting signal. Chemical cross-linking together with immunoelectron microscopy show that the mitochondrial APP exists in NH2-terminal inside transmembrane orientation and in contact with mitochondrial translocase proteins. Mutational studies show that the acidic domain, which spans sequence 220-290 of APP, causes the transmembrane arrest with the COOH-terminal 73-kD portion of the protein facing the cytoplasmic side. Accumulation of full-length APP in the mitochondrial compartment in a transmembrane-arrested form, but not lacking the acidic domain, caused mitochondrial dysfunction and impaired energy metabolism. These results show, for the first time, that APP is targeted to neuronal mitochondria under some physiological and pathological conditions.

Alzheimer Disease↗
PubMedDate not supplied

Effects of peroxidized polyunsaturated fatty acids on mitochondrial function and structure: pathogenetic implications for Reye's syndrome.

Linoleic acid, a polyunsaturated fatty acid, is a constituent of margosa oil which has been implicated as a cause of Reye's syndrome (RS) in infants. Increased concentrations of polyunsaturated fatty acids have been found in sera from patients with RS. Isolated rat liver mitochondria exposed to the peroxidized (but not unperoxidized) methyl esters of linoleic (C18:2) or linolenic (C18:3) acids showed decreases in state 3 and uncoupled respiratory rates and in respiratory control and ADP/O ratios. In addition, they caused mitochondrial swelling as demonstrated spectrophotometrically. Between the two, the peroxidized methyl ester of linolenic acid was more toxic and was capable of inducing high amplitude swelling ultrastructurally similar to that seen in the hepatocytes of RS victims. The ability of rat liver mitochondria to oxidize glutamate was inversely related to the peroxide concentration in the medium. This accords with the reports of reduced glutamic dehydrogenase activities in the livers of both patients with Reye's syndrome and rats treated with margosa oil.

Animals↗