Decrease in cytochrome c oxidase reserve capacity diminishes robustness of Drosophila melanogaster and shortens lifespan

2014 ◽  
Vol 459 (1) ◽  
pp. 127-135 ◽  
Author(s):  
Vladimir Klichko ◽  
Barbara H. Sohal ◽  
Svetlana N. Radyuk ◽  
William C. Orr ◽  
Rajindar S. Sohal
Keyword(s):  
Drosophila Melanogaster ◽  
Electron Transport ◽  
Cytochrome C ◽  
Structure Function ◽  
Cytochrome C Oxidase ◽  
Electron Transport Chain ◽  
Reserve Capacity ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain

The suppression of cytochrome c oxidase function exerts deleterious rather than benign effects on fitness and survival. The structure/function of cytochrome c oxidase, a mitochondrial electron-transport chain oxidoreductase, can be re-engineered in vivo.

scholarly journals Anticancer gold(iii)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition

2021 ◽  
Author(s):  
Jong Hyun Kim ◽  
Samuel Ofori ◽  
Sean Parkin ◽  
Hemendra Vekaria ◽  
Patrick G. Sullivan ◽  
...  
Keyword(s):  
Electron Transport ◽  
Metal Complexes ◽  
Electron Transport Chain ◽  
Chemical Diversity ◽  
Mitochondrial Electron Transport Chain ◽  
Generate Functional ◽  
Tumor Inhibition ◽  
Transport Chain

Expanding the chemical diversity of metal complexes provides a robust platform to generate functional bioactive reagents.

scholarly journals Effects of L-Malate on Mitochondrial Oxidoreductases in Liver of Aged Rats

2011 ◽  
pp. 329-336 ◽  
Author(s):  
J.-L. WU ◽  
Q.-P. WU ◽  
Y.-P. PENG ◽  
J.-M. ZHANG
Keyword(s):  
Electron Transport ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Electron Transport Chain ◽  
Nadh Dehydrogenase ◽  
Tricarboxylic Acid Cycle ◽  
Radical Scavenger ◽  
Aged Rats ◽  
Transport Chain ◽  
Nadh Cytochrome

Accumulation of oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the aging process. The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-malate, a tricarboxylic acid cycle intermediate, plays an important role in transporting NADH from cytosol to mitochondria for energy production. Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. In the present study we focused on the effect of L-malate on the activities of electron transport chain in young and aged rats. We found that mitochondrial membrane potential (MMP) and the activities of succinate dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats were significantly decreased when compared to young control rats. Supplementation of L-malate to aged rats for 30 days slightly increased MMP and improved the activities of NADH-dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats when compared with aged control rats. In young rats, L-malate administration increased only the activity of NADH-dehydrogenase. Our result suggested that L-malate could improve the activities of electron transport chain enzymes in aged rats

scholarly journals Oxidative and non-oxidative mechanisms in the inactivation of cardiac mitochondrial electron transport chain components by doxorubicin

1989 ◽  
Vol 259 (1) ◽  
pp. 181-189 ◽  
Author(s):  
O Marcillat ◽  
Y Zhang ◽  
K J A Davies
Keyword(s):  
Electron Transport ◽  
Cytochrome C ◽  
Oxidative Damage ◽  
Cytochrome C Oxidase ◽  
Electron Transport Chain ◽  
Nadh Dehydrogenase ◽  
Nadh Oxidase ◽  
Redox Cycling ◽  
Oxidative Inactivation ◽  
Transport Chain

The quinonoid anthracycline, doxorubicin (Adriamycin) is a potent anti-neoplastic agent whose clinical use is limited by severe cardiotoxicity. Mitochondrial damage is a major component of this cardiotoxicity, and rival oxidative and non-oxidative mechanisms for inactivation of the electron transport chain have been proposed. Using bovine heart submitochondrial preparations (SMP) we have now found that both oxidative and non-oxidative mechanisms occur in vitro, depending solely on the concentration of doxorubicin employed. Redox cycling of doxorubicin by Complex I of the respiratory chain (which generates doxorubicin semiquinone radicals, O2-, H2O2, and .OH) caused a 70% decrease in the Vmax. for NADH dehydrogenase during 15 min incubation of SMP, and an 80% decrease in NADH oxidase activity after 2 h incubation. This inactivation required only 25-50 microM-doxorubicin and represents true oxidative damage, since both NADH (for doxorubicin redox cycling) and oxygen were obligatory participants. The damage appears localized between the NADH dehydrogenase flavin (site of doxorubicin reduction) and iron-sulphur centre N-1. Succinate dehydrogenase, succinate oxidase, and cytochrome c oxidase activities were strongly inhibited by higher doxorubicin concentrations, but this phenomenon did not involve doxorubicin redox cycling (no NADH or oxygen requirement). Doxorubicin concentrations of 0.5 mM were required for 50% decreases in these activities, except for cytochrome c oxidase which was only 30% inhibited following incubation with even 1.0 mM-doxorubicin. Our results indicate that low concentrations of doxorubicin (50 microM or less) can catalyse a site-specific oxidative damage to the NADH oxidation pathway. In contrast, ten-fold higher doxorubicin concentrations (or more) are required for non-oxidative inactivation of the electron transport chain; probably via binding to cardiolipin and/or generalized membrane chaotropic effects. The development of agents to block doxorubicin toxicity in vivo will clearly require detailed clinical studies of doxorubicin uptake in the heart.

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