Control of the nitric oxide-cytochrome c oxidase signaling pathway under pathological and physiological conditions

Prominent among the mechanisms of interaction of nitric oxide (NO) with intracellular targets are the reactions with heme proteins. For example, the mechanism through which NO induces synthesis of the second messenger cyclic GMP involves the binding of NO to the heme in soluble guanylate cyclase. It has only recently been appreciated that NO binding to the binuclear oxygen binding site in cytochrome c oxidase may also serve as a signal transduction pathway. We postulate that NO is uniquely positioned to control mitochondrial respiration and in doing so regulates oxygen gradients within the cell. In this short overview the mechanisms of NO-dependent regulation of mitochondrial function will be discussed in the context of some of the biological and physiological consequences.