Mitochondrial membrane potential supported by exogenous cytochrome c oxidation mimics the early stages of apoptosis

Mitochondria isolated from rat liver, incubated with inhibitors of respiratory Complexes I and III but in the presence of added NADH as a source of reducing equivalents, generate a membrane potential, the extent of which is comparable to that supported by the oxidation of intramitochondrial respiratory substrates. A catalytic amount of exogenously added cytochrome c is required in order for this membrane potential to be observed. Such an experimental approach mimics the early stages of the apoptotic program of mammalian cells. This has been reported to be characterized by the extrusion of the bulk of intermembrane pool of cytochrome c while the mitochondria continue to preserve their membrane potential. The data obtained are consistent with the proposal that the bi-trans-membrane electron transport pathway, activated by the transfer of cytochrome c from mitochondria to the cytosolic compartment, may be directly involved in the generation of the mitochondrial membrane potential at the beginning of the cell death process