Synergistical effect of NO and Ca2+ on mitochondrial function

Abstract

Nitric oxide (NO) and Ca2+ concentration in tissue is reported to increase during various myocardial pathologies, including ischemia. In this study, we investigated the effect of 4 μM NO on isolated rat heart mitochondria in the presence of 5 μM of free Ca2+, conditions resembling the ischemic situation. We found NO together with Ca2+ to inhibit the NAD-substrate oxidation pathway due to inactivation of Complex I. Inhibition of Complex I was prevented by superoxidedismutase and urate, and reversed by light and thiols, suggesting the inhibition that might occur due to nitrosation of some critical thiols by peroxynitrite. Keywords: mitochondria, nitric oxide, respiration, nitrosation, Complex I, peroxynitrite