Inhibition of mitochondrial electron transport and energy transduction by 2-methyl-4-dimethylaminoazobenzene in vitro.

2-Methyl-4-dimethylaminoazobenzene (I) [54-88-6] inhibited electron transport and phosphorylation in tightly coupled rat liver mitochondria. It stimulated state 4 respiration, decreased ADP/O ratio, inhibited state 3 oxidation and abolished respiratory control. These effects reveal its action as an inhibitor uncoupler. Consistent with its preferential inhibition of the NADH-ubiquinone segment of the respiratory chain, ferricyanide reduction was far more sensitive to inhibition by I when NAD+-linked substrates were used as electron donors than when succinate was used. Like a true uncoupler, it stimulated the dormant ATPase [9000-83-3] activity in tightly coupled mitochondria in the presence and absence of Mg. However, in the absence of added Mg, dinitrophenol-stimulated activity was drastically inhibited indicating its action as a membrane destabilizing agent. In sonic submitochondrial particles, I inhibited energy-linked reverse electron transport and transhydrogenase reaction.