Inhibitory effect of t-butyl hydroperoxide on mitochondrial oxidative phosphorylation in isolated rat hepatocytes

Abstract

Using high-resolution oxygraphy we tested changes of various parameters characterizing the mitochondrial energy provision system that were induced by oxidative damage.In the presence of succinate as respiratory substrate,3 mM t-butyl hydroperoxide increased respiration in the absence of ADP,which indicated partial uncopling of oxidative phosphorylation.Low activity of coupled respiration was still maintained.However,during the incubation the phosphorylative capacity decreased as indicated by the continous decrease of the mitochondrial membrane potential.Under these experimental conditions the maximum capacity of the succinate oxidase system was inhibited by 50% in comparison with values obtained in the absence of t-butyl hydroperoxide.Our data thus indicate that the oxygraphic evaluation of mitochondrial function represents a useful tool for evaluation of changes participating in peroxidative damage of cell energy metabolism.