Effects of 2,4,3′,5′-tetrahydroxystilbene on oxidative phosphorylation by rat liver mitochondria

Abstract

The effects of an antifungal compound 2,4,3′,5′-tetrahydroxystilbene (THS)† on oxidative phosphorylation by rat liver mitochondria were studied. THS at low concentrations was found to inhibit state 3 respiration (I 50 = 44 nmoles/mg protein) but had no effect on uncoupled respiration induced by 2,4-dinitrophenol. The inhibitory effect of THS on state 3 respiration was observed with either glutamate or succinate as respiratory substrates. However when rat liver mitochondria were respiring with glutamate as substrate and in the presence of calcium chloride and inorganic phosphate, THS produced a strong inhibition of 2,4-dinitrophenol-stimulated respiration. This inhibition was over-come by adding succinate. The tetramethoxy derivative of THS had no effect on the mitochondrial reactions mentioned above suggesting that the phenolic groups are essential for the action of THS. The sites at which THS inhibits mitochondrial oxidative phosphorylation are proposed. © 1976.