title: The regulation of mitochondrial oxygen uptake by redox reactions involving nitric oxide and ubiquinol.
abstract: 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) 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) 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.
authors.affiliation: Laboratory of Oxygen Metabolism, University Hospital, School of Medicine, University of Buenos Aires, Córdoba 2351, 1120 Buenos Aires, Argentina.jpoderos@fmed.uba.ar
authors.forename: J J
authors.initials: JJ
authors.lastname: Poderoso
authors.forename: C
authors.initials: C
authors.lastname: Lisdero
authors.forename: F
authors.initials: F
authors.lastname: Schöpfer
authors.forename: N
authors.initials: N
authors.lastname: Riobó
authors.forename: M C
authors.initials: MC
authors.lastname: Carreras
authors.forename: E
authors.initials: E
authors.lastname: Cadenas
authors.forename: A
authors.initials: A
authors.lastname: Boveris
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D008930:Mitochondria, Liver / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D014451:Ubiquinone; D009569:Nitric Oxide; C003741:ubiquinol; D010100:Oxygen