Increasing evidences have shown the existance of a mitochondrial nitric oxide synthase(mtNOS),which binds to the matrix face of the mitochondrial inner membrane and produces nitric oxide(NO) through a Ca~(2+)sensitive pathway.Under physiological condition,the NO catalyzed by mtNOS regulates mitochondrial oxygen consumption and transmembrane potential via reversible competition with cytochrome C oxidase.The reaction of NO with superoxide anion,which was produced by mitochondrial respiratory chain,yields peroxynitrite.Peroxynitrite irreversibly modifies susceptible targets in mitochondria and induces oxidative and/or nitrative stress.In addition,NO has also been implicated in the programmed cell death.This article reviews the current understanding of mtNOS's role in the regulation of mitochondrial functions.