The effect of nitric oxide on mitochondrial respiration

This article reviews the interactions between nitric oxide (NO) and mitochondrial respiration. Mitochondrial ATP synthesis is responsible for virtually all energy production in mammals, and every other process in living organisms ultimately depends on that energy production. Furthermore, both necrosis and apoptosis, that summarize the main forms of cell death, are intimately linked to mitochondrial integrity. Endogenous and exogenous center dot NO inhibits mitochondrial respiration by different well-studied mechanisms and several nitrogen derivatives. Instantaneously, low concentrations of center dot NO, specifically and reversibly inhibit cytochrome c oxidase in competition with oxygen, in several tissues and cells in culture. Higher concentrations of center dot NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain, uncoupling, permeability transition, and/or cell death. Peroxynitrite can cause opening of the permeability transition pore and opening of this pore causes loss of cytochrome c, which in turn might contribute to peroxynitrite-induced inhibition of respiration. Therefore, the inhibition of cytochrome c oxidase by center dot NO may be involved in the physiological and/or pathological regulation of respiration rate, and its affinity for oxygen, which depend on reactive nitrogen species formation, pH, proton motriz force and oxygen supply to tissues.