The formation of peroxynitrite in the applied physiology of mitochondrial nitric oxide.
Mitochondria require nitric oxide ((.)NO) to exert a delicate control of metabolic rate as well as to regulate life functions, cell cycle activation and arrest, and apoptosis. All activities depend on the matrical (.)NO steady state concentration as provided by mitochondrial (mtNOS) and cytosolic sources (eNOS) and reduced by forming superoxide anion and H2O2 and a low peroxynirite (ONOO(-)) yield. We review herein the biochemical pathways involved in the control of (.)NO mitochondrial level and its biological and physiological significance in hormone effects and aging. At high ()NO, the cost of this physiological regulation is that ONOO(-) excess will lead to nitrosation/nitration and oxidization of mitochondrial and cell proteins and lipids. The disruption of (.)NO modulation of mitochondrial respiration supports then, a platform for prevalent neurodegenerative and metabolic diseases.
Poderoso
Juan J
JJ
Director of the Laboratory of Oxygen Metabolism, University Hospital, CONICET and University of Buenos Aires, Córdoba 2351, 1120 Buenos Aires, Argentina. jpoderos@fmed.uba.ar
D000375:Aging / Q000502:physiology; D000818:Animals; D006801:Humans; D007328:Insulin / Q000502:physiology; D020738:Leptin / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010101:Oxygen Consumption; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013961:Thyroid Gland / Q000502:physiology
D007328:Insulin; D020738:Leptin; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase