Nitric oxide and peroxynitrite interactions with mitochondria.
Nitric oxide (*NO) and peroxynitrite (ONOO-) avidly interact with mitochondrial components, leading to a range of biological responses spanning from the modulation of mitochondrial respiration, mitochondrial dysfunction to the signaling of apoptotic cell death. Physiological levels of *NO primarily interact with cytochrome c oxidase, leading to a competitive and reversible inhibition of mitochondrial oxygen uptake. In turn, this leads to alterations in electrochemical gradients, which affect calcium uptake and may regulate processes such as mitochondrial transition pore (MTP) opening and the release of pro-apoptotic proteins. Large or persistent levels of *NO in mitochondria promote mitochondrial oxidant formation. Peroxynitrite formed either extra- or intra-mitochondrially leads to oxidative damage, most notably at complexes I and II of the electron transport chain, ATPase, aconitase and Mn-superoxide dismutase. Mitochondrial scavenging systems for peroxynitrite and peroxynitrite-derived radicals such as carbonate (CO3*-) and nitrogen dioxide radicals (*NO2) include cytochrome c oxidase, glutathione and ubiquinol and serve to partially attenuate the reactions of these oxidants with critical mitochondrial targets. Detection of nitrated mitochondrial proteins in vivo supports the concept that mitochondria constitute central loci of the toxic effects of excess reactive nitrogen species. In this review we will provide an overview of the biochemical mechanisms by which *NO and ONOO- regulate or alter mitochondrial functions.
Radi
Rafael
R
Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. rradi@fmed.edu.uy
Cassina
Adriana
A
Hodara
Roberto
R
D000818:Animals; D004579:Electron Transport; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism*
D005609:Free Radicals; D030421:Peroxynitrous Acid; D009569:Nitric Oxide