scholarly journals Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment

2004 ◽  
Vol 382 (2) ◽  
pp. 491-499 ◽  
Author(s):  
Damien ROUSSEL ◽  
Jean-François DUMAS ◽  
Gilles SIMARD ◽  
Yves MALTHIÈRY ◽  
Patrick RITZ
Keyword(s):  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Liver Mitochondria ◽  
Energetic Cost ◽  
Proton Leak ◽  
Mitochondrial Bioenergetics ◽  
Dexamethasone Treatment ◽  
And Control

The present investigation was undertaken in order to evaluate the contributions of ATP synthesis and proton leak reactions to the rate of active respiration of liver mitochondria, which is altered following dexamethasone treatment (1.5 mg/kg per day for 5 days). We applied top-down metabolic control analysis and its extension, elasticity analysis, to gain insight into the mechanisms of glucocorticoid regulation of mitochondrial bioenergetics. Liver mitochondria were isolated from dexamethasone-treated, pair-fed and control rats when in a fed or overnight fasted state. Injection of dexamethasone for 5 days resulted in an increase in the fraction of the proton cycle of phosphorylating liver mitochondria, which was associated with a decrease in the efficiency of the mitochondrial oxidative phosphorylation process in liver. This increase in proton leak activity occurred with little change in the mitochondrial membrane potential, despite a significant decrease in the rate of oxidative phosphorylation. Regulation analysis indicates that mitochondrial membrane potential homoeostasis is achieved by equal inhibition of the mitochondrial substrate oxidation and phosphorylation reactions in rats given dexamethasone. Our results also suggest that active liver mitochondria from dexamethasone-treated rats are capable of maintaining phosphorylation flux for cellular purposes, despite an increase in the energetic cost of mitochondrial ATP production due to increased basal proton permeability of the inner membrane. They also provide a complete description of the effects of dexamethasone treatment on liver mitochondrial bioenergetics.

scholarly journals Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Carsten Esselun ◽  
Bastian Bruns ◽  
Stephanie Hagl ◽  
Rekha Grewal ◽  
Gunter P. Eckert
Keyword(s):  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Membrane Potential ◽  
Cell Lines ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Nitrosative Stress ◽  
Citrate Synthase ◽  
Atp Levels ◽  
Age Related

The Mediterranean plant Silybum marianum L., commonly known as milk thistle, has been used for centuries to treat liver disorders. The flavonolignan silibinin represents a natural antioxidant and the main bioactive ingredient of silymarin (silybin), a standard extract of its seeds. Mitochondrial dysfunction and the associated generation of reactive oxygen/nitrogen species (ROS/RNS) are involved in the development of chronic liver and age-related neurodegenerative diseases. Silibinin A (SIL A) is one of two diastereomers found in silymarin and was used to evaluate the effects of silymarin on mitochondrial parameters including mitochondrial membrane potential and ATP production with and without sodium nitroprusside- (SNP-) induced nitrosative stress, oxidative phosphorylation, and citrate synthase activity in HepG2 and PC12 cells. Both cell lines were influenced by SIL A, but at different concentrations. SIL A significantly weakened nitrosative stress in both cell lines. Low concentrations not only maintained protective properties but also increased basal mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels. However, these effects could not be associated with oxidative phosphorylation. On the other side, high concentrations of SIL A significantly decreased MMP and ATP levels. Although SIL A did not provide a general improvement of the mitochondrial function, our findings show that SIL A protects against SNP-induced nitrosative stress at the level of mitochondria making it potentially beneficial against neurological disorders.

Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding

2000 ◽  
Vol 349 (2) ◽  
pp. 519-526 ◽  
Author(s):  
Ausra MARCINKEVICIUTE ◽  
Vida MILDAZIENE ◽  
Sara CRUMM ◽  
Oleg DEMIN ◽  
Jan B. HOEK ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Rat Liver ◽  
Liver Mitochondria ◽  
Proton Leak ◽  
Rat Liver Mitochondria ◽  
Protonmotive Force ◽  
Compensatory Mechanisms ◽  
Mitochondrial Energy Metabolism ◽  
Ethanol Feeding ◽  
And Control

Changes in the kinetics and regulation of oxidative phosphorylation were characterized in isolated rat liver mitochondria after 2 months of ethanol consumption. Mitochondrial energy metabolism was conceptually divided into three groups of reactions, either producing protonmotive force (∆p) (the respiratory subsystem) or consuming it (the phosphorylation subsystem and the proton leak). Manifestation of ethanol-induced mitochondrial malfunctioning of the respiratory subsystem was observed with various substrates; the respiration rate in State 3 was inhibited by 27±4% with succinate plus amytal, by 20±4% with glutamate plus malate, and by 17±2% with N,N,Nʹ,Nʹ-tetramethyl-p-phenylenediamine/ascorbate. The inhibition of the respiratory activity correlated with the lower activities of cytochrome c oxidase, the bc1 complex, and the ATP synthase in mitochondria of ethanol-fed rats. The block of reactions consuming the ∆p to produce ATP (the phosphorylating subsystem) was suppressed after 2 months of ethanol feeding, whereas the mitochondrial proton leak was not affected. The contributions of ∆p supply (the respiratory subsystem) and ∆p demand (the phosphorylation and the proton leak) to the control of the respiratory flux were quantified as the control coefficients of these subsystems. In State 3, the distribution of control exerted by different reaction blocks over respiratory flux was not significantly affected by ethanol diet, despite the marked changes in the kinetics of individual functional units of mitochondrial oxidative phosphorylation. This suggests the operation of compensatory mechanisms, when control redistributes among the different components within the same subsystem.

scholarly journals T-2307 Causes Collapse of Mitochondrial Membrane Potential in Yeast

2012 ◽  
Vol 56 (11) ◽  
pp. 5892-5897 ◽  
Author(s):  
Tatsuya Shibata ◽  
Toshinari Takahashi ◽  
Eio Yamada ◽  
Akiko Kimura ◽  
Hiroshi Nishikawa ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Rat Liver ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Liver Mitochondria ◽  
Yeast Cells ◽  
Rat Liver Mitochondria ◽  
Content Type ◽  
Glycerol Medium

ABSTRACTT-2307, an arylamidine compound, has been previously reported to have broad-spectrumin vitroandin vivoantifungal activities against clinically significant pathogens, includingCandidaspecies,Cryptococcus neoformans, andAspergillusspecies, and is now undergoing clinical trials. Here we investigated the mechanism of action of T-2307 using yeast cells and mitochondria isolated from yeast and rat liver. Nonfermentative growth ofCandida albicansandSaccharomyces cerevisiaein glycerol medium, in which yeasts relied on mitochondrial respiratory function, was inhibited at 0.001 to 0.002 μg/ml (0.002 to 0.004 μM) of T-2307. However, fermentative growth in dextrose medium was not inhibited by T-2307. Microscopic examination using Mitotracker fluorescent dye, a cell-permeant mitochondrion-specific probe, demonstrated that T-2307 impaired the mitochondrial function ofC. albicansandS. cerevisiaeat concentrations near the MIC in glycerol medium. T-2307 collapsed the mitochondrial membrane potential in mitochondria isolated fromS. cerevisiaeat 20 μM. On the other hand, in isolated rat liver mitochondria, T-2307 did not have any effect on the mitochondrial membrane potential at 10 mM. Moreover, T-2307 had little inhibitory and stimulatory effect on mitochondrial respiration in rat liver mitochondria. In conclusion, T-2307 selectively disrupted yeast mitochondrial function, and it was also demonstrated that the fungal mitochondrion is an attractive antifungal target.

scholarly journals Role of Mitochondrial Dynamics in Microglial Activation and Metabolic Switch

2021 ◽  
Author(s):  
Alejandro Montilla ◽  
Asier Ruiz ◽  
Mar Marquez ◽  
Amanda Sierra ◽  
Carlos Matute ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Microglial Activation ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Metabolic Reprogramming ◽  
Metabolic Switch

Abstract Microglia act as sensors of injury in the brain, favouring its homeostasis. Their activation and polarization towards a pro-inflammatory phenotype are associated to injury and disease. These processes are linked to a metabolic reprogramming of the cells, characterized by high rates of glycolysis and suppressed oxidative phosphorylation. This metabolic switch can be reproduced in vitro by microglial stimulation with lipopolysaccharide (LPS) plus interferon-γ (IFNγ). In order to understand the mechanisms regulating mitochondrial respiration abolishment, we examined potential alterations in mitochondrial features during this switch. Cells did not show any change in mitochondrial membrane potential, suggesting a limited impact in the mitochondrial viability. We provide evidence that reverse operation of F0F1-ATP synthase contributes to mitochondrial membrane potential. In addition, we studied the possible implication of mitochondrial dynamics in the metabolic switch using the mitochondrial division inhibitor-1 (Mdivi-1), which blocks Drp1-dependent mitochondrial fission. Mdivi-1 significantly reduced the expression of pro-inflammatory markers in LPS+IFNγ-treated microglia. However, this inhibition did not lead to a recovery of the oxidative phosphorylation ablation by LPS+IFNγ or to a microglia repolarization. Altogether, these results suggest that Drp1-dependent mitochondrial fission, although potentially involved in microglial activation, does not play an essential role in metabolic reprogramming and repolarization of microglia.

Primary causes of decreased mitochondrial oxygen consumption during metabolic depression in snail cells

2002 ◽  
Vol 282 (2) ◽  
pp. R372-R382 ◽  
Author(s):  
Tammie Bishop ◽  
Julie St-Pierre ◽  
Martin D. Brand
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Respiration ◽  
Mitochondrial Membrane ◽  
Substrate Oxidation ◽  
Proton Leak ◽  
Mitochondrial Oxygen Consumption ◽  
Atp Turnover ◽  
Hypometabolic State ◽  
Kinetics Of

Cells isolated from the hepatopancreas of estivating snails ( Helix aspersa) have strongly depressed mitochondrial respiration compared with controls. Mitochondrial respiration was divided into substrate oxidation (which produces the mitochondrial membrane potential) and ATP turnover and proton leak (which consume it). The activity of substrate oxidation (and probably ATP turnover) decreased, whereas the activity of proton leak remained constant in estivation. These primary changes resulted in a lower mitochondrial membrane potential in hepatopancreas cells from estivating compared with active snails, leading to secondary decreases in respiration to drive ATP turnover and proton leak. The respiration to drive ATP turnover and proton leak decreased in proportion to the overall decrease in mitochondrial respiration, so that the amount of ATP turned over per O2 consumed remained relatively constant and aerobic efficiency was maintained in this hypometabolic state. At least 75% of the total response of mitochondrial respiration to estivation was caused by primary changes in the kinetics of substrate oxidation, with only 25% or less of the response occurring through primary effects on ATP turnover.

scholarly journals Myrica rubraExtracts Protect the Liver from CCl4-Induced Damage

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Lizhi Xu ◽  
Jing Gao ◽  
Yucai Wang ◽  
Wen Yu ◽  
Xiaoning Zhao ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Liver Mitochondria ◽  
Mitochondrial Outer Membrane ◽  
Free Calcium ◽  
Dependent Manner ◽  
Protective Effects ◽  
Nuclear Condensation ◽  
Serum Aspartate Aminotransferase

The relationship between the expression of mitochondrial voltage-dependent anion channels (VDACs) and the protective effects ofMyrica rubraSieb. Et Zucc fruit extract (MCE) against carbon tetrachloride (CCl4)-induced liver damage was investigated. Pretreatment with 50 mg kg−1, 150 mg kg−1or 450 mg kg−1MCE significantly blocked the CCl4-induced increase in both serum aspartate aminotransferase (sAST) and serum alanine aminotransferase (sALT) levels in mice (P< .05 or .01 versus CCl4group). Ultrastructural observations of decreased nuclear condensation, ameliorated mitochondrial fragmentation of the cristae and less lipid deposition by an electron microscope confirmed the hepatoprotection. The mitochondrial membrane potential dropped from −191.94 ± 8.84 mV to −132.06 ± 12.26 mV (P< .01) after the mice had been treated with CCl4. MCE attenuated CCl4-induced mitochondrial membrane potential dissipation in a dose-dependent manner. At a dose of 150 or 450 mg kg−1of MCE, the mitochondrial membrane potentials were restored (P< .05). Pretreatment with MCE also prevented the elevation of intra-mitochondrial free calcium as observed in the liver of the CCl4-insulted mice (P< .01 versus CCl4group). In addition, MCE treatment (50–450 mg kg−1) significantly increased both transcription and translation of VDAC inhibited by CCl4. The above data suggest that MCE mitigates the damage to liver mitochondria induced by CCl4, possibly through the regulation of mitochondrial VDAC, one of the most important proteins in the mitochondrial outer membrane.

scholarly journals Goa1p of Candida albicans Localizes to the Mitochondria during Stress and Is Required for Mitochondrial Function and Virulence

2009 ◽  
Vol 8 (11) ◽  
pp. 1706-1720 ◽  
Author(s):  
Adrienne Bambach ◽  
Mariana P. Fernandes ◽  
Anup Ghosh ◽  
Michael Kruppa ◽  
Deepu Alex ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Fluorescent Protein ◽  
Human Neutrophils ◽  
Agar Media ◽  
Green Fluorescent

ABSTRACT Using a Tn7 transposon library of Candida albicans, we have identified a mutant that exhibited sensitivity in drop plate assays to oxidants such as menadione and hydrogen peroxide. To verify the role of the mutated gene in stress adaptation, null mutants were constructed and phenotypically characterized. Because of its apparent functions in growth and oxidant adaptation, we have named the gene GOA1. Goa1p appears to be unique to the CTG subclade of the Saccharomycotina, including C. albicans. Mutants of C. albicans lacking goa1 (strain GOA31) were more sensitive to 6 mM H2O2 and 0.125 mM menadione than the wild type (wt) or a gene-reconstituted (GOA32) strain. The sensitivity to oxidants correlated with reduced survival of the GOA31 mutant in human neutrophils and avirulence compared to control strains. Other phenotypes of GOA31 include reduced growth and filamentation in 10% serum, Spider, and SLAD agar media and an inability to form chlamydospores. Since Goa1p has an N-terminal mitochondrion localization site, we also show that green fluorescent protein-tagged Goa1p shows a mitochondrionlike distribution during oxidant or osmotic stress. Further, the inability of GOA31 to grow in medium containing lactate, ethanol, or glycerol as the sole carbon source indicates that the mitochondria are defective in the mutant. To determine how Goa1p contributes to mitochondrial function, we compared the wt, GOA32, and GOA31 strains for mitochondrial electrical membrane potential, respiration, and oxidative phosphorylation. We now show that GOA31, but not the wt or GOA32, had decreased respiration and mitochondrial membrane potential such that mutant cells are unable to drive oxidative phosphorylation. This is the first report in C. albicans of a respiratory defect caused by a loss of mitochondrial membrane potential.

Hepatoprotection of Oleanolic Acid is Related to Its Inhibition on Mitochondrial Permeability Transition

2005 ◽  
Vol 33 (04) ◽  
pp. 627-637 ◽  
Author(s):  
Xin-Hui Tang ◽  
Jing Gao ◽  
Feng Fang ◽  
Jin Chen ◽  
Li-Zhi Xu ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Oleanolic Acid ◽  
Mitochondrial Membrane ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Mitochondrial Swelling ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mitochondrial Membrane Depolarization

The protective effects of oleanolic acid (OA) on carbon tetrachloride (CCl4)-induced liver mitochondrial damage and the possible mechanisms were investigated. Pretreatment with OA prior to the administration of CCl4 significantly suppressed the increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (4.2- and 19.9-fold, respectively) in a dose-dependent manner in mice. The dissipation of mitochondrial membrane potential (14.8%) and intra-mitochondrial Ca 2+ overload (2.1-fold) in livers of CCl4-insulted mice were also dose-dependently prevented by pretreatment with 20, 50 or 100 mg/kg OA. In addition, the effects of OA on liver mitochondria permeability transition (MPT) induced by Ca 2+ were assessed by measuring the change in mitochondrial membrane potential, release of matrix Ca 2+ and mitochondrial swelling in vitro. The results showed that preincubation with 50 or 100 μg/ml OA obviously inhibited the Ca 2+-induced mitochondrial swelling, mitochondrial membrane depolarization and intra-mitochondrial Ca 2+ release. It could be concluded that OA has protective effects on liver mitochondria and the mechanisms underlying its protection may be related to its inhibitory action on MPT.

scholarly journals Simultaneous evaluation of substrate-dependent oxygen consumption rates and mitochondrial membrane potential by TMRM and safranin in cortical mitochondria

2016 ◽  
Vol 36 (1) ◽  
Author(s):  
Subir Roy Chowdhury ◽  
Jelena Djordjevic ◽  
Benedict C. Albensi ◽  
Paul Fernyhough
Keyword(s):  
Oxygen Consumption ◽  
Membrane Potential ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Mitochondrial Bioenergetics ◽  
Respiration Rates ◽  
Pathological Conditions ◽  
Simultaneous Evaluation ◽  
Consumption Rates

Simultaneous evaluation of two mitochondrial bioenergetics parameters, respiration rates and mitochondrial membrane potential (mtMP) can be useful to determine the mitochondrial dysfunction under various pathological conditions including neurodegenerative diseases and diabetes.

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