Original contribution
Aging, cytochrome oxidase activity, and hydrogen peroxide release by mitochondria

https://doi.org/10.1016/0891-5849(93)90139-LGet rights and content

Abstract

The objective of this study was to explore the possible cause(s) underlying the previously observed, age-related increase in the rate of mitochondrial H2O2 release in the housefly. The hypothesis that an imbalance between different respiratory complexes may be a causal factor was tested. Cytochrome c oxidase activity was found to sharply decline in the latter part of the life span of the flies. Effects of different substrates and respiratory inhibitors were determined in order to ascertain if a decrease in cytochrome c oxidase activity could be responsible for the increased H2O2 release. H2O2 was measured spectrofluorometrically using horseradish peroxidase and p-hydrophenylacetate as an indicator. Neither NADH-linked substrates nor succinate caused a stimulation of H2O2 production. H2O2 release by mitochondria, inhibited with rotenone and antimycin A, was greatly increased upon supplementation with α-glycerophosphate; however, the further addition of KCN or myxothiazol, to such preparations, caused a depression of H2O2 generation. In contrast, relatively low concentrations of KCN or myxothiazol were found to stimulate H2O2 release in insect mitochondria supplemented with α-glycerophosphate and exposed to rotenone, but not antimycin A. Results are interpreted to suggest that partial inhibition of cytochrome c oxidase activity can lead to the stimulation of mictochondrial H2O2 production in the housefly at site(s) other than NADH dehydrogenase and ubisemiquinone/ cytochrome b region; a possible source may be glycerophosphate dehydrogenase.

References (30)

Cited by (128)

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    Citation Excerpt :

    Inhibition of this step by myxothiazol has an effect on the ROS production rate that is identical to the effect of AA in model L (Fig. 5B,D) which is compatible with experimental observations of the myxothiazol effect on ROS production in liver mitochondria [71]. However, there are experimental observations in rat heart and brain [70] and insect muscle [86] mitochondria which showed a smaller increase in ROS production induced by myxothiazol alone than AA alone. Moreover, these observations show inhibition of the ROS production rate by myxothiazol in the presence of AA.

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This research was supported by grant RO1AG7657 from the National Institutes of Health—National Institute on Aging.

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