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The influence of nitric oxide on mitochondrial permeability transition (MPT) phenomenon was studied. NO was generated by photolysis of S-nitroso-N-acetylcysteine, AcCys(NO), with green light (2 = 550 nm). Two distinct effects of nitric oxide on rat liver mitochondria were identified. First, NO accelerated an onset of swelling in Caz'-loaded mitochondria in a cyclosporin-A-sensitive manner acting as an inducer of permeability transition. This was, apparently, a result of irreversible alteration of mitochondrial function accompanying the inhibition of respiratory chain in the presence of calcium. Formation of ESR-visible iron-sulfur dinitrosyl complexes (g = 2.041) could also contribute to the irreversible changes resulting in MPT induction. Second, NO changed significantly the response of mitochondria to Ca'+/phosphate-induced MPT, acting as a regulator of permeability transition. In this case the action of nitric oxide led to division of the mitochondria into two subpopulations: one which underwent the rapid permeability transition and another in which the MPT was inhibited. The effect of NO on Ca2+/Pi-induced MPT was transient and resulted from reversible inhibition of cytochrome oxidase followed by the changes in transmembrane potential and Ca2+ distribution. The characteristic time of duration of these NO modulated effects depended on nitric oxide as well as on oxygen concentrations. With increasing NO at fixed oxygen concentrations, this time levelled off to reach a maximum value which was inversely related to the oxygen concentration. It is concluded that under physiological condition the duration of reversible NO effects on mitochondrial function could be determined by oxygen concentration.Keywords: nitric oxide ; mitochondrial permeability transition.Nitric oxide (NO) plays multiple roles in diverse physiological processes, including relaxation of smooth muscle, neurotransmission, inhibition of platelet aggregation and killing of pathogens [l]. At the present time a large body of evidence has accumulated suggesting an important role of NO and peroxynitrite (the product of NO interaction with superoxide) in modulation of mitochondrial function. It has been shown that nitric oxide can reversibly inhibit mitochondrial respiration by competing with oxygen at cytochrome oxidase [2, 31. On the other hand, the fonnation of peroxynitrite from NO and mitochondria-derived superoxide can cause the irreversible inhibition of complexes 1-111 leading to mitochondrial dysfunction [4, 51. It has been proposed that NO exerts some of its main physiological and pathological effects by shifting ATP/ADP due to inhibition of respiratory chain [6]. It has also been shown that nitric oxide influences the mitochondrial Caz+ metabolism. Thus both NO and peroxynitrite are able to induce mitochondrial Ca*+ efflux by distinct and apparently specific pathways 17, 81. Calcium efflux induced by nitric oxide could contribute significantly to cellular damage during NO overproduction [9].It is now generally believed that mitochondrial C...

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