The regulation of mitochondrial oxygen uptake by redox reactions involvingnitric oxide and ubiquinol

The reversible inhibitory effects of nitric oxide (. NO) on mitochondrial c ytochrome oxidase and O-2 uptake are dependent on intramitochondrial . NO u tilization. This study was aimed at establishing the mitochondrial pathways for . NO utilization that regulate O-2(radical anion) generation via reduc tive and oxidative reactions involving ubiquinol oxidation and peroxynitrit e (ONOO-) formation. For this purpose, experimental models consisting of in tact mitochondria, ubiquinone-depleted/reconstituted submitochondrial parti cles, and ONOO--supplemented mitochondrial membranes were used. The results obtained from these experimental approaches strongly suggest th e occurrence of independent pathways for . NO utilization in mitochondria, which effectively compete with the binding of . NO to cytochrome oxidase, t hereby releasing this inhibition and restoring O-2 uptake. The pathways for . NO utilization are discussed in terms of the steady-state levels of . NO and O-2(radical anion) and estimated as a function of O-2 tension. These c alculations indicate that mitochondrial . NO decays primarily by pathways i nvolving ONOO- formation and ubiquinol oxidation and, secondarily, by rever sible binding to cytochrome oxidase.