Nitric oxide induces superoxide anion release by reacting with ubiquinol in mitochondrial membranes

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Previously, we have reported that nitric oxide (NO) is able to react in vitro with ubiquinol to produce nitroxyl anion and a semiquinone and, in the presence of O2, superoxide anion (O2-). To test whether the reaction could take place in mitochondria and mitochondrial membranes, the organelles were isolated from Sprague Dawley rat liver by differential centrifugation and submitochondrial particles by sonication. Mitochondria and membranes were supplemented with ubiquinone-0 (Q-0) and ubiquinone-2 (Q-2) incorporation to membranes was tested by spectra consistent with complete reduction of Q to QH2 in the presence of 1 mM NADH. Addition of authentic NO induced reoxidation of membrane solubilized quinine. In addition, inhibition of mitochondrial O2 uptake and of cytochrome oxidase with 5 µM NO was dose-dependent reversed by addition of either 2-30 µM Q-0 or Q-2. In accord, the production of mitochondrial H2O2, in the presence of NO was increased from 0.14 to 0.22 nmoles min-1.mg-1prot. NO deenergized mitochondrial membranes; the lowering in electrochemical potential (DY) was reverted iin the presence of succinate in a linear correlation with H2O2 production. The results indicate that 1. NO-QH2 reaction takes place in mitochondria, 2. effects of NO on the membranes are reverted by this reaction and are dependent of ubiquinol concentration, and 3. mitochondrial production of O2- is probably destined to control NO effects. Información suministrada por el agente en SIGEVA