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.