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Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation.
- Source :
-
The Biochemical journal [Biochem J] 2001 Oct 01; Vol. 359 (Pt 1), pp. 139-45. - Publication Year :
- 2001
-
Abstract
- This study was aimed at assessing the effects of long-term exposure to NO of respiratory activities in mitochondria from different tissues (with different ubiquinol contents), under conditions that either promote or prevent the formation of peroxynitrite. Mitochondria and submitochondrial particles isolated from rat heart, liver and brain were exposed either to a steady-state concentration or to a bolus addition of NO. NO induced the mitochondrial production of superoxide anions, hydrogen peroxide and peroxynitrite, the latter shown by nitration of mitochondrial proteins. Long-term incubation of mitochondrial membranes with NO resulted in a persistent inhibition of NADH:cytochrome c reductase activity, interpreted as inhibition of NADH:ubiquinone reductase (Complex I) activity, whereas succinate:cytochrome c reductase activity, including Complex II and Complex III electron transfer, remained unaffected. This selective effect of NO and derived species was partially prevented by superoxide dismutase and uric acid. In addition, peroxynitrite mimicked the effect of NO, including tyrosine nitration of some Complex I proteins. These results seem to indicate that the inhibition of NADH:ubiquinone reductase (Complex I) activity depends on the NO-induced generation of superoxide radical and peroxynitrite and that Complex I is selectively sensitive to peroxynitrite. Inhibition of Complex I activity by peroxynitrite may have critical implications for energy supply in tissues such as the brain, whose mitochondrial function depends largely on the channelling of reducing equivalents through Complex I.
- Subjects :
- Animals
Brain drug effects
Electron Transport drug effects
Electron Transport Complex I
Electron Transport Complex II
Female
Heart drug effects
Hydrogen Peroxide metabolism
Immunoblotting
Liver drug effects
Mitochondria drug effects
Mitochondria, Heart drug effects
NAD metabolism
NADH, NADPH Oxidoreductases metabolism
Rats
Rats, Sprague-Dawley
Succinate Cytochrome c Oxidoreductase metabolism
Succinates metabolism
Superoxide Dismutase metabolism
Tyrosine metabolism
Mitochondria enzymology
Multienzyme Complexes metabolism
NADH, NADPH Oxidoreductases antagonists & inhibitors
Nitric Oxide pharmacology
Oxidoreductases metabolism
Peroxynitrous Acid metabolism
Succinate Dehydrogenase metabolism
Superoxides metabolism
Tyrosine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 359
- Issue :
- Pt 1
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 11563977
- Full Text :
- https://doi.org/10.1042/0264-6021:3590139