Inhibition of succinate-linked respiration and complex II activity by hydrogen peroxide

Hydrogen peroxide produced from electron transport chain derived superoxide is a relatively mild oxidant, and as such, the majority of mitochondrial enzyme activities are impervious to physiological concentrations. Previous studies, however, have suggested that complex II (succinate dehydrogenase) is sensitive to H2O2-mediated inhibition. Nevertheless, the effects of H2O2 on succinate-linked respiration and complex II activity have not been examined in intact mitochondria. Results presented indicate that H2O2 inhibits succinate-linked state 3 mitochondrial respiration in a concentration dependent manner. H2O2 has no effect on complex II activity during state 2 respiration, but inhibits activity during state 3. It was found that conditions which prevent oxaloacetate accumulation during state 3 respiration, such as inclusion of rotenone, glutamate, or ATP, blunted the effect of H2O2 on succinate-linked respiration and complex II activity. It is concluded that H2O2 inhibits succinate-linked respiration indirectly by sustaining and enhancing oxaloacetate-mediated inactivation of complex II.