The formation of peroxynitrite in the applied physiology of mitochondrial nitric oxide |
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Authors: | Juan J Poderoso |
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Institution: | Director of the Laboratory of Oxygen Metabolism, University Hospital, CONICET and University of Buenos Aires, Córdoba 2351, 1120 Buenos Aires, Argentina |
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Abstract: | 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. |
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Keywords: | Nitric oxide Peroxynitrite Mitochondria Mitochondrial nitric oxide synthase Insulin Thyroid hormones Aging Nitration Oxygen uptake ob&minus /ob&minus mice |
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