The existence and significance of a mitochondrial nitrite reductase.
The physiological functions of nitric oxide (NO) are well established. The finding that the endothelium-derived relaxing factor (EDRF) is NO was totally unexpected. It was shown that NO is a reaction product of an enzymatically catalyzed, overall, 5-electron oxidation of guanidinium nitrogen from L-arginine followed by the release of the free radical species NO. NO is synthesized by a single protein complex supported by cofactors, coenzymes (such as tetrahydrobiopterin) and cytochrome P450. The latter can uncouple from substrate oxidation producing O2*- radicals. The research groups of Richter [Ghafourifar P, Richter C. Nitric oxide synthase activity in mitochondria. FEBS Lett 1997; 418: 291-296.] and Boveris [Giulivi C, Poderoso JJ, Boveris A. Production of nitric oxide by mitochondria. J Biol Chem 1998; 273: 11038-11043.] identified a mitochondrial NO synthase (NOS). There are, however, increasing reports demonstrating that mitochondrial NO is derived from cytosolic NOS belonging to the Ca2+-dependent enzymes. NO was thought to control cytochrome oxidase. This assumption is controversial due to the life-time of NO in biological systems (millisecond range). We found a nitrite reductase in mitochondria which is of major interest. Any increase of nitrite in the tissue which is the first oxidation product of NO, for instance following NO donors, will stimulate NO-recycling via mitochondrial nitrite reductase. In this paper, we describe the identity and the function of mitochondrial nitrite reductase and the consequences of NO-recycling in the metabolic compartment of mitochondria.
Nohl
Hans
H
Research Institute for Biochemical Pharmacology and Toxicology, University of Veterinary Medicine of Vienna, Vienna, Austria. hans.nohl@vu-wien.ac.at
Staniek
Katrin
K
Kozlov
Andrey V
AV
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009572:Nitrite Reductases / Q000737:chemistry*; D009573:Nitrites / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D013367:Submitochondrial Particles / Q000737:chemistry
D045462:Endothelium-Dependent Relaxing Factors; D009573:Nitrites; D016877:Oxidants; D000968:Antimycin A; D001120:Arginine; D009572:Nitrite Reductases; D003576:Electron Transport Complex IV; D010100:Oxygen