Mitochondrial nitric oxide synthase, oxidative stress and apoptosis.
Nitric oxide (NO) exerts a wide range of its biological properties via its interaction with mitochondria. By competing with O(2), physiologically relevant concentrations of NO reversibly inhibit cytochrome oxidase and decrease O(2) consumption, in a manner resembling a pharmacological competitive antagonism. The inhibition regulates many cellular functions, by e.g., regulating the synthesis of ATP and the formation of mitochondrial transmembrane potential (Delta Psi). NO regulates the oxygen consumption of both the NO-producing and the neighboring cells; thus, it can serve as autoregulator and paracrine modulator of the respiration. On the other hand, NO reacts avidly with superoxide anion (O(2)(-)) to produce the powerful oxidizing agent, peroxynitrite (ONOO(-)) which affects mitochondrial functions mostly in an irreversible manner. How mitochondria and cells harmonize the reversible effects of NO versus the irreversible effects of ONOO(-) will be discussed in this review article. The exciting recent finding of mitochondrial NO synthase will also be discussed.
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01545, USA. pedram.ghafourifar@umassmed.edu
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Bringold
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Klein
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Richter
D017209:Apoptosis; D008928:Mitochondria / Q000201:enzymology*; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects
D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase