Fatty acid-induced Ca(2+)-dependent uncoupling and activation of external pathway of NADH oxidation are coupled to cyclosporin A-sensitive mitochondrial permeability transition.

Permeabilization of inner mitochondrial membrane by palmitic acid in the presence of Ca2+ (cyclosporin A-sensitive stimulation of respiration, decrease of delta psi and high amplitude swelling) is accompanied by activation of the external pathway of NADH oxidation in liver mitochondria. The "pore"-sealing agents (cyclosporin A, Mg2+ with ADP, and L-carnitine with ATP) are equally effective in preventing the induction of external pathway of NADH oxidation by Ca2+ with palmitate. However, activities of these agents are different in respect to recoupling of permeabilized mitochondria. Participation of cyclosporin A-sensitive "pore" in the fatty acid- and Ca(2+)-dependent induction of external pathway of NADH oxidation and in Ca(2+)-dependent uncoupling is discussed.