Anisotropic inhibition of energy transduction in oxidative phosphorylation in rat liver mitochondria by tetraphenylarsonium.

Tetraphenylarsonium (TPA+) inhibited energy transduction in oxidative phosphorylation in mitochondria but not in submitochondrial particles, which are inside-out relative to the membranes of mitochondria. TPA+ incorporated into the inside of submitochondrial particles inhibited ATP synthesis in the particles. TPA+ also inhibited the reduction of NAD by succinate coupled with oxidation of succinate by O2 and hydrolysis of ATP. Energization of mitochondrial inner membranes with succinate and with ATP induced binding sites on the membranes for TPA+. The amounts of energy-dependent binding sites for TPA+ on mitochondria energized with succinate and with ATP, respectively, were 90 and 13 nmol/mg of protein. TPA+ also caused shrinkage of mitochondria energized with succinate and with ATP in an energy-dependent fashion. The energy-dependent binding of TPA+, TPA+-induced H+-ejection, TPA+-induced shrinkage of mitochondria, and TPA+-induced inhibition of energy transduction occurred in parallel. The present findings show that TPA+ inhibits energy transduction by binding to negative charges created on lipophilic domains near the surface of the outer side (C-side) of the mitochondrial inner membranes, and that it has no inhibitory activity on the inner side (M-side) of the membranes.