UC Davis

Nitric oxide is generated in vivo by nitric-oxide synthase (NOS) during the conversion of L-Arg to citrulline. Using a variety of biological systems and approaches emerging evidence has been accumulated for the occurrence of a mitochondrial NOS (mtNOS), identified as the alpha isoform of neuronal or NOS-1. Under physiological conditions, the production of nitric oxide by mitochondria has an important implication for the maintenance of the cellular metabolism, i.e. modulates the oxygen consumption of the organelles through the competitive (with oxygen) and reversible inhibition of cytochrome c oxidase. The transient inhibition suits the continuously changing energy and oxygen requirements of the tissue; it is a short-term regulation with profound pathophysiological consequences. This review describes the identification of mtNOS and the role of posttranslational modifications on mtNOS' activity and regulation.