Mechanism of the inhibitory action of capsaicin on energy metabolism by rat liver mitochondria

Abstract

Capsaicin was found to inhibit the oxidation of exogenous NADH by digitonin particles and hypotonic-treated rat liver mitochondria without impairing the oxidation of succinate by these mitochondrial preparations. The action of methyl capsaicin, the non-phenolic derivative of capsaicin, on mitochondrial oxidative phosphorylation and NADH oxidation was found identical to that of capsaicin. However, on the basis of I 50, values, methyl capsaicin was approximately three times more potent. The inhibition of NADH oxidation produced by capsaicin and its methylated derivative was completely relieved by addition of menadione, an electron acceptor at the NADH dehydrogenase segment of mitochondrial electron transport chain. From these observations, it is concluded that (a) both capsaicin and methyl capsaicin inhibit mitochondrial energy metabolism by retarding electrons flow from NADH to coenzyme Q; (b) the location of this action is beyond the site at which menadione accepts electrons from the NADH dehydrogenase system; and (c) the phenolic group in capsaicin molecule is not essential for the above mitochondrial action of this compound.