Myxothiazol induces H2O2 production from mitochondrial respiratory chain

Interruption of electron flow at the quinone-reducing center (Q(i)) of comp lex III of the mitochondrial respiratory chain results in superoxide produc tion. Unstable semiquinone bound in quinol-oxidizing center (Q(o)) of compl ex In: is thought to be the sole source of electrons for oxygen reduction; however, the unambiguous evidence is lacking We investigated the effects of complex III inhibitors antimycin, myxothiazol, and stigmatellin on generat ion of H2O2 in rat heart and brain mitochondria. In the absence of antimyci n A, myxothiazol stimulated H2O2 production by mitochondria oxidizing malat e, succinate, or cr-glycerophosphate. Stigmatellin inhibited H2O2 productio n induced by myxothiazol. Myxothiazol-induced H2O2 production was dependent on the succinate/fumarate ratio but in a manner different from H2O2 genera tion induced by antimycin A. We conclude that myxothiazol-induced H2O2 orig inates from a site located in the complex III Q(o) center but different fro m the site of H2O2 production inducible by antimycin A (C) 2001 Academic Pr ess.