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Results for “Mitochondrial function”

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PubMed1996

Opposite effects of metallothionein I and spermine on mitochondrial function.

Previously, we reported that the stress-induced protein metallothionein I (MT) modulated the oxygen consumption (VO2) of isolated rat liver mitochondria [Life Sci. 55 221-226, 1994]. We now present confirmation of this finding, and the additional observations that in rat liver mitochondria, MT caused swelling and depolarization. These actions of MT were inhibited by the aliphatic polyamine, spermine. Our findings suggest that mitochondrial function could be influenced by the balance between MT and spermine.

Animals↗

PubMed1997

Preconditioning preserves mitochondrial function and glycolytic flux during an early period of reperfusion in perfused rat hearts.

OBJECTIVE: The purpose of the present study was to examine the effects of preconditioning on glycolysis and oxidative phosphorylation during reperfusion in perfused rat hearts. METHODS: Preconditioning was induced by 5 min of ischemia and 5 min of reperfusion before 40 min of sustained ischemia and subsequent 30 min of reperfusion. Tissue energy metabolite levels, mitochondrial oxygen consumption capacity and adenine nucleotide translocator content of the perfused hearts were assessed at 40 min of ischemia, 5 and 30 min of reperfusion. RESULTS: Preconditioning improved the postischemic recovery of rate x pressure product (92.5 +/- 8.7 vs. 24.9 +/- 1.2% for non-preconditioned group) and high-energy phosphate content (ATP and CrP; 39.5 +/- 2.0 and 96.2 +/- 4.9% of initial vs. 24.1 +/- 0.9 and 56.1 +/- 4.3% of initial for the non-preconditioned group). The mitochondrial oxygen consumption capacity and the adenine nucleotide translocator content of the non-preconditioned heart were decreased by sustained ischemia and remained decreased throughout reperfusion. Preconditioning prevented these decreases. The tissue lactate level of the non-preconditioned heart was high throughout reperfusion (16.5-fold vs. basal), whereas in the preconditioned heart it returned to the basal level within a few minutes of reperfusion. Furthermore, the ratios of [fructose 1,6-bisphosphate]/([glucose 6-phosphate] + [fructose 6-phosphate]) at 5-min reperfusion were higher (2.2-fold) than those of the non-preconditioned heart. CONCLUSIONS: The results suggest that preconditioning preserves the capacity for normal mitochondrial function and the facilitation of glycolysis during reperfusion, which may play an important role in the improvement of postischemic contractile function and high-energy phosphate content.

Adenosine Triphosphate↗

PubMed2003

Disruption of mitochondrial function in Candida albicans leads to reduced cellular ergosterol levels and elevated growth in the presence of amphotericin B.

A respiratory-deficient mutant of Candida albicans MEN was generated by culturing cells in medium supplemented with ethidium bromide at 37 degrees C for 5 days. The respiratory-deficient mutant (C. albicans MMU11) was incapable of growth on glycerol, had a reduced oxygen uptake rate and demonstrated an altered mitochondrial cytochrome profile. Respiratory-competent cybrids were formed by mitochondrial transfer following fusion of protoplasts with those of C. albicans ATCC 44990. Mutant MMU11 possessed lower levels of ergosterol than the parental isolates and the cybrids, and demonstrated a small but statistically significant increase in tolerance to amphotericin B. The results demonstrated that disruption of mitochondrial function in C. albicans increases the tolerance to amphotericin B, possibly mediated by a reduction in cellular ergosterol content.

Amphotericin B↗

PubMed2006

Caloric restriction protects mitochondrial function with aging in skeletal and cardiac muscles.

In skeletal muscles and heart in vitro complex IV activity is lower in young adult caloric restricted (CR) animals despite normal aerobic function in situ and in vivo. On the other hand, whereas markers of oxidative capacity decline 25% to 46% between 8 and 10 months and 35 months in ad libitum fed (AL) animals, in most muscles there is no decline in CR across the same absolute age (35 mo old) or relative age (35% survival rate) span and PGC-1alpha gene expression in gastrocnemius muscle declines more slowly with aging. The present results show that CR largely prevents the age-associated decline in mitochondrial function in heart and skeletal muscles, and suggest that this is secondary to a better-maintained drive on mitochondrial biogenesis.

Aging↗

PubMed1995

Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function.

During ischemic brain injury, glutamate accumulation leads to overstimulation of postsynaptic glutamate receptors with intracellular Ca2+ overload and neuronal cell death. Here we show that glutamate can induce either early necrosis or delayed apoptosis in cultures of cerebellar granule cells. During and shortly after exposure to glutamate, a subpopulation of neurons died by necrosis. In these cells, mitochondrial membrane potential collapsed, nuclei swelled, and intracellular debris were scattered in the incubation medium. Neurons surviving the early necrotic phase recovered mitochondrial potential and energy levels. Later, they underwent apoptosis, as shown by the formation of apoptotic nuclei and by chromatin degradation into high and low molecular weight fragments. These results suggest that mitochondrial function is a critical factor that determines the mode of neuronal death in excitotoxicity.

Animals↗

PubMed1968

Cortisone-induced alterations in mitochondrial function and structure.

The effects of cortisone treatment on oxygen consumption, oxidative phosphorylation, and fine structure of rat liver mitochondria have been studied. Male rats weighing 125 g were treated for 6 days with 5 mg of cortisone acetate or isotonic saline. On the 7th day, sections of liver were excised and processed for light and electron microscopy. Mitochondrial respiration and oxidative phosphorylation were studied with mitochondria isolated from these livers. Cortisone treatment is responsible for a 14-40% decrease in the amount of oxygen consumed per mg of mitochondrial protein when succinate, alpha-ketoglutarate, or beta-hydroxybutyrate are used as substrates, or with ascorbate and N,N,N(1),N(1)-tetramethyl p-phenylenediamine as electron donors. In addition, oxidative phosphorylation is uncoupled with a lowering of the P:O ratios. Randomly selected liver cells have been analyzed by quantitative morphometric techniques. The average mitochondrial volume is increased fourfold in the peripheral and midzonal regions with a commensurate decrease in the number of mitochondria per cell. These alterations are present throughout the hepatic lobule, but are most marked in midzonal cells. The total mitochondrial volume per cell and the per cent of the total cytoplasmic volume occupied by mitochondria remains relatively unaltered, as does the total amount of cristae surface per cell. While the mitochondria are enlarged, they are not "swollen." The relationships between the steroid hormone treatment and the alterations in mitochondrial function and structure are discussed.

Animals↗

PubMed2002

Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases.

We show here the transient activation of the small GTPase Rac, followed by a rise in reactive oxygen species (ROS), as necessary early steps in a signal transduction cascade that lead to NFkappaB activation and collagenase-1 (CL-1)/matrix metalloproteinase-1 production after integrin-mediated cell shape changes. We show evidence indicating that this constitutes a new mechanism for ROS production mediated by small GTPases. Activated RhoA also induced ROS production and up-regulated CL-1 expression. A Rac mutant (L37) that prevents reorganization of the actin cytoskeleton prevented integrin-induced CL-1 expression, whereas mutations that abrogate Rac binding to the neutrophil NADPH membrane oxidase in vitro (H26 and N130) did not. Instead, ROS were produced by integrin-induced changes in mitochondrial function, which were inhibited by Bcl-2 and involved transient membrane potential loss. The cells showing this transient decrease in mitochondrial membrane potential were already committed to CL-1 expression. These results unveil a new molecular mechanism of signal transduction triggered by integrin engagement where a global mitochondrial metabolic response leads to gene expression rather than apoptosis.

Animals↗

PubMed1987

Effects of dietary selenium on lipid peroxidation, mitochondrial function and protein profiles in the heart of the myopathic Syrian golden hamster (BIO 14.6).

Male, weanling myopathic Syrian Golden Hamsters (BIO 14.6 strain) were fed a selenium-adequate diet (controls) or this diet supplemented with 1.0 ppm selenium (treated) for 30 days. Se-treated animals exhibited a 50% reduction in lipid peroxidation in heart homogenates relative to controls and a 61% increase in mitochondrial glycerophosphate acyltransferase activity. Gel electrophoresis revealed no alterations in cardiac protein profiles from treated or control animals. These data suggest that the selenium prevents peroxidative injury and maintains mitochondrial function in the absence of alterations in cardiac proteins.

Animals↗

PubMed1991

Yeast CBP1 mRNA 3' end formation is regulated during the induction of mitochondrial function.

Alternative mRNA processing is one mechanism for generating two or more polypeptides from a single gene. While many mammalian genes contain multiple mRNA 3' cleavage and polyadenylation signals that change the coding sequence of the mature mRNA when used at different developmental stages or in different tissues, only one yeast gene has been identified with this capacity. The Saccharomyces cerevisiae nuclear gene CPB1 encodes a mitochondrial protein that is required for cytochrome b mRNA stability. This 66-kDa protein is encoded by a 2.2-kb mRNA transcribed from CPB1. Previously we showed that a second 1.2-kb transcript is initiated at the CBP1 promoter but has a 3' end near the middle of the coding sequence. Furthermore, it was shown that the ratio of the steady-state level of 2.2-kb CBP1 message to 1.2-kb message decreases 10-fold during the induction of mitochondrial function, while the combined levels of both messages remain constant. Having proposed that regulation of 3' end formation dictates the amount of each CBP1 transcript, we now show that a 146-bp fragment from the middle of CBP1 is sufficient to direct carbon source-regulated production of two transcripts when inserted into the yeast URA3 gene. This fragment contains seven polyadenylation sites for the wild-type 1.2-kb mRNA, as mapped by sequence analysis of CBP1 cDNA clones. Deletion mutations upstream of the polyadenylation sites abolished formation of the 1.2-kb transcript, whereas deletion of three of the sites only led to a reduction in abundance of the 1.2-kb mRNA. Our results indicate that regulation of the abundance of both CBP1 transcripts is controlled by elements in a short segment of the gene that directs 3' end formation of the 1.2-kb transcript, a unique case in yeast cells.

Base Sequence↗

PubMed2004

Perfluorocarbon emulsion improves cerebral oxygenation and mitochondrial function after fluid percussion brain injury in rats.

OBJECTIVE: Cerebral ischemia is a common secondary sequela of traumatic brain injury (TBI). Experimental models of stroke have demonstrated reductions in ischemia after perfluorocarbon (PFC) administration; however, there are no published reports of PFC efficacy after TBI. The current study analyzed the effect of the PFC emulsion Oxygent (AF0144; Alliance Pharmaceutical Corp., San Diego, CA) on cerebral oxygenation, mitochondrial redox potential, and free radical formation after lateral fluid percussion injury. METHODS: After fluid percussion injury, five 2.25 ml/kg doses of PFC or saline were administered to rats breathing 100% O(2), and oxygen tension was recorded. In a second experiment, a single bolus (11.25 ml/kg) of PFC or saline was given after injury, and redox potential and free radical formation were measured at 1 or 4 hours with Alamar blue dye and dihydrorhodamine 123, respectively. RESULTS: Cerebral oxygen tension was significantly increased in both injured and sham animals treated with 11.25 ml/kg of PFC as compared with saline (P < 0.05). Likewise, PFC significantly increased mitochondrial redox potential as compared with saline at 4 hours after injury (P < 0.01). Mitochondrial peroxynitrite and peroxide production also increased with the administration of PFC (P < 0.05). CONCLUSION: The current study demonstrates that a PFC emulsion can significantly increase cerebral oxygenation after TBI and enhance mitochondrial function at 4 hours after injury as compared with saline. This study demonstrates a new therapeutic potential for PFC to enhance cerebral oxygenation and aerobic metabolism after TBI. However, the increased free radical formation with high-dose PFCs suggests the need for further studies combining PFCs with free radical scavengers.

Animals↗

PubMed1979

Mitochondrial function and free fatty acid levels in rats after portacaval shunt.

The effects of portacaval shunting on the oxidative phosphorylation process of mitochondria isolated from rat liver and skeletal muscle were evaluated and correlated with mitochondria free fatty acid (FFA) contents. ADP/O ratios, respiratory control index and QO2 values were significantly depressed in liver mitochondria from portacaval-shunted rats; these changes were associated with decreased mitochondrial FFA contents. The mitochondrial function of skeletal muscle was unaltered.

Animals↗

PubMed1987

Mitochondrial function in brain tissue in primary degenerative dementia.

Previous in vitro and in vivo studies of the brain in Alzheimer's disease indicated alterations in metabolism related to energy production although the relationships between these changes remains obscure. To help resolve this issue, in vitro oxygen uptake by homogenates of fresh samples of frontal neocortex from patients with dementia and neurosurgical controls has been examined as a measure of energy-related metabolism and mitochondrial function. Maximal respiratory rates (measured in the presence of an uncoupling agent) were similar for samples from 7 controls, 5 patients with Alzheimer's disease and two patients diagnosed clinically as Pick's disease, suggesting that there was little or no effect of these dementias on the maximal metabolic capacity of the tissue. However, under some conditions producing sub-maximal metabolic activity (which are of potentially greater physiological relevance) oxygen uptake rates were significantly elevated in the dementia group. The ratio of oxygen uptake rates in the presence and absence of ADP was significantly reduced (to 58% of control; P less than 0.02) for the dementia patients compared with controls, possibly indicative of partial mitochondrial uncoupling. These results indicate metabolic changes expressed in vitro which may be relevant to the pathogenesis of Alzheimer's disease and some related dementias.

Alzheimer Disease↗

PubMed1991

The nuclear coded mitoribosomal proteins YmL27 and YmL31 are both essential for mitochondrial function in yeast.

Using synthetic oligonucleotides deduced from the N-terminal amino acid sequence of purified mitoribosomal protein (mt r-protein) YmL27, the corresponding nuclear gene MRP-L27 of the yeast Saccharomyces cerevisiae has been cloned and sequenced. The MRP-L27 gene codes for 146 amino acids and is located on chromosome X. The mature YmL27 protein consists of 130 amino acids - after cleaving the putative mitochondrial signal peptide - with a net charge of +17 and a calculated relative molecular mass of 14,798 Da. The YmL27 protein as well as the yeast mitoribosomal protein YmL31, which had been characterized and its gene (MRP-L31) cloned previously, is essential for mitochondrial function as shown by the inability of gene disrupted mutants for the MRP-L27 or MRP-L31 genes to grow on non-fermentable carbon sources.

Amino Acid Sequence↗

PubMed1983

Effects of hormones on the maintenance and mitochondrial functions of rat hepatocytes cultured in serum-free medium.

The survival and morphology of rat hepatocytes were examined in primary cell cultures that were maintained in serum-free medium supplemented with different hormones. Insulin and dexamethasone improved survival and maintenance of normal epithelial-shaped cells, although triiodothyronine did not alter cell survival or morphology when added to the medium alone or with other hormones. The level of mitochondrial alpha-glycerophosphate dehydrogenase and cytochromes a(+a3), b and c, but not c1, were increased in cultured hepatocytes by triiodothyronine. Although induction of alpha-glycerophosphate dehydrogenase did not require serum or growth hormone, the triiodothyronine effect was potentiated by insulin plus dexamethasone. This permissive effect of dexamethasone parallels its known glucocorticoid action of increasing the activity of the gluconeogenic enzyme tyrosine aminotransferase in the cultured hepatocytes. Glucagon, which also elevated tyrosine aminotransferase activity, had no effect upon the induction of alpha-glycerophosphate dehydrogenase by triiodothyronine. Since the culture medium was completely defined and triiodothyronine did not alter survival or morphology of the hepatocytes, the effects upon mitochondrial functions are direct cellular actions of the thyroid hormone.

Animals↗

PubMed2005

Mitochondrial function, energy expenditure, aging and insulin resistance.

Mitochondria are the cells' powerhouse that produce the ubiquitous energy currency (ATP) by consuming oxygen, producing water and building up the proton motive force. Oxygen consumption is a classical means of assessing energy expenditure, one component of energy balance. When energy balance is positive, weight increases. This is observed during the dynamic phase of obesity, and during body composition changes associated with aging. Whether intrinsic defaults in mitochondria occur is the matter of this review. Indeed, the ratio of ATP over oxygen consumed, which is not fixed, is one way of regulating heat release and ATP flux, but can also be the consequence of environmental conditions of mitochondrial work. For example, various hormones (T3, glucocorticoids), changes in lipid membrane composition, changes in food intake and exercise, and various drugs, can modify the ratio of ATP over oxygen consumed. Aging and insulin resistance are other regulators of this ratio. Finally there is a rising body of evidence linking diabetes to mitochondrial functions.

Aged↗

PubMed1997

Mitochondrial function is involved in LDL oxidation mediated by human cultured endothelial cells.

Human endothelial cells (ECs) grown under standard conditions are able to generate a basal level of oxygen free radicals and induce progressive oxidation of LDLs. Inhibition of cell-mediated LDL oxidation by superoxide dismutase, EDTA, or desferrioxamine implicates a role for superoxide anion and/or transition metals in this process. The potential role of the mitochondrion was investigated by inducing mitochondrial deenergization by selective photosensitization or the addition of inhibitors of the mitochondrial respiratory chain. Mitochondria of human cultured ECs were selectively damaged by photosensitization of cells labeled with the mitochondrion-selective fluorescent dye 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide under conditions that induced only low levels of toxicity during the time of the experiment. Photosensitized ECs exhibited severe mitochondrial dysfunction, as suggested by the defect in mitochondrial uptake of the mitochondrion-selective fluorescent dyes [rhodamine 123 and 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide] and morphological alterations as shown by transmission electron microscopy. In mitochondria-photosensitized cells, superoxide anion generation was strongly decreased, as was LDL oxidation and the subsequent cytotoxicity. When ECs were incubated with the mitochondrial respiratory-chain inhibitors antimycin A or rotenone or with the carbonylcyanide-m-chlorophenylhydrazone uncoupler rhodamine 123, uptake and subcellular distribution were altered, and concomitantly superoxide anion production and LDL oxidation were strongly decreased. In conclusion, these data suggest that mitochondrial function is required, directly or indirectly, for the production of superoxide anion and the subsequent LDL oxidation by human vascular ECs.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗

PubMed2000

Alternative mitochondrial functions in cell physiopathology: beyond ATP production.

It is well known that mitochondria are the main site for ATP generation within most tissues. However, mitochondria also participate in a surprising number of alternative activities, including intracellular Ca2+ regulation, thermogenesis and the control of apoptosis. In addition, mitochondria are the main cellular generators of reactive oxygen species, and may trigger necrotic cell death under conditions of oxidative stress. This review concentrates on these alternative mitochondrial functions, and their role in cell physiopathology.

Adenosine Triphosphate↗

PubMed2002

The evaluation of brain CBF and mitochondrial function by a fiber optic tissue spectroscope in neurosurgical patients.

The brain of neurosurgical patients are exposed to various manipulations in the ICU or during surgery. Under such conditions brain O2 balance may become negative and as a result brain vitality and function will deteriorate. In order to evaluate brain vitality in real time it is important to measure more than one parameter. The multiparametric monitoring system used in our previous study to monitor comatose patients (Mayevsky et al., Brain Res. 740: 268-274, 1996) was changed into a "simplified" tissue spectroscope for real time monitoring of brain O2 balance. Mitochondrial function was evaluated by monitoring the NADH redox state by surface fluorometry. Microcirculatory blood flow was assessed by laser Doppler flowmetry. The combined optical probe was located on the surface of the brain during various neurosurgical procedures and the responses were recorded and presented in real time to the surgeon. A total of 32 patients were monitored during various procedures. The results could be summarized as follows: 1. Hypercapnia led to 3 different types of responses. In two patients the 'stealing' like event was recorded. In the other 7 patients the responses to high CO2 was not detectable. In the last group of 6 patients a clear CBF elevation was recorded with variable response of mitochondrial NADH. 2. Our monitoring device was able to evaluate the efficacy of the STA-MCA anastomosis during aneurysm surgery. 3. A significant correlation was recorded between CBF and NADH redox state during changes in blood pressure, papaverine injection, spontaneous drop in blood supply to the brain or during releasing of high ICP levels. We conclude that in order to evaluate the metabolic state of the brain during neurosurgical procedures it is necessary to monitor both CBF and mitochondrial NADH by using the tissue spectroscope.

Brain↗