Glutathione and the mitochondrial reduction of hydroperoxides

Various organic hydroperoxides are reduced when added to rat liver mitochondrial suspensions. Succinate increases the rate and duration of the reductions except for linoleic acid hydroperoxide which appears to inhibit its own reduction. 3-Hydroxybutyrate replaces succinate but other reductants used are less effective. The rate of reduction of tert-butyl hydroperoxide by succinate is not inhibited by cyanide but is partly inhibited if antimycin or rotenone are also added; ATP reverses the antimycin inhibition. Other inhibitors include the uncoupler, carbonyl cyanide p-trifluoromethoxyhydrazone, ADP + Pi, the thiol reagents N-ethylmaleimide and p-hydroxymercuribenzoate and inhibitors of the mitochondrial transport of carboxylic acids. In some cases, the GSH concentration of the mitochondria during the reductions correlates with the reduction rate (e.g. with succinate and after N-ethylmaleimide) but in others it is dissociated. The results suggest that hydroperoxide reduction requires the GSH-glutathione peroxidase pathway but that entry of the oxidants into the mitochondrial matrix is also an energy-dependent step.