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

The reversible inhibitory effects of nitric oxide (. NO) on mitochondrial cytochrome oxidase and O-2 uptake are dependent on intramitochondrial . NO utilization. This study was aimed at establishing the mitochondrial pathways for . NO utilization that regulate O-2(radical anion) generation via reductive and oxidative reactions involving ubiquinol oxidation and peroxynitrite (ONOO-) formation. For this purpose, experimental models consisting of intact mitochondria, ubiquinone-depleted/reconstituted submitochondrial particles, and ONOO--supplemented mitochondrial membranes were used. The results obtained from these experimental approaches strongly suggest the occurrence of independent pathways for . NO utilization in mitochondria, which effectively compete with the binding of . NO to cytochrome oxidase, thereby 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 calculations indicate that mitochondrial . NO decays primarily by pathways involving ONOO- formation and ubiquinol oxidation and, secondarily, by reversible binding to cytochrome oxidase.