Electron transport inhibition of the cytochrome bc1 complex of rat-liver mitochondria by phenolic uncouplers.

The respiration inhibition of rat-liver mitochondria by a series of substituted phenolic uncouplers was studied. The inhibitory effects were classified into three types, I-III, depending on the pattern of the changes in inhibitory potency observed when the potent uncoupler SF6847 was simultaneously applied. The extent of inhibition by type I phenols did not change as the transmembrane potential was dissipated by SF6847, but the extent of inhibition by type II and III phenols was decreased and increased, respectively. With the addition of another potent uncoupler, fluazinam, the uncoupling activity of which disappears with time, the inhibitory potency of type II phenols was decreased, but increased reversibly with the disappearance of the uncoupling effect of fluazinam. However, the inhibitory potency of type III phenols increased by fluazinam was not reduced. The inhibitory site of the phenols studied here was the cytochrome bc1 complex. This complex undergoes conformational changes when the transmembrane potential changes. The findings suggested that inhibition by substituted phenolic uncouplers depends partially on conformational changes of the cytochrome bc1 complex that accompany variations in the transmembrane potential.