A major pathway of nitric oxide utilization in mitochondria is its conversion to peroxynitrite, a species involved in biomolecule damage via oxidation, hydroxylation and nitration reactions. In the present study the potential role of mitochondrial ubiquinol in protecting against peroxynitrite-mediated damage is examined and the requirements of the mitochondrial redox status that support this function of ubiquinol are established. (1) Absorption and EPR spectroscopy studies revealed that the reactions involved in the ubiquinol/peroxynitrite interaction were first-order in peroxynitrite and zero-order in ubiquinol, in agreement with the rate-limiting formation of a reactive intermediate formed during the isomerization of peroxynitrite to nitrate. Ubiquinol oxidation occurred in one-electron transfer steps as indicated by the formation of ubisemiquinone. (2) Peroxynitrite promoted, in a concentration-dependent manner, the formation of superoxide anion by mitochondrial membranes. (3) Ubiquinol protected against peroxynitrite-mediated nitration of tyrosine residues in albumin and mitochondrial membranes, as suggested by experimental models, entailing either addition of ubiquinol or expansion of the mitochondrial ubiquinol pool caused by selective inhibitors of complexes III and IV. (4) Increase in membrane-bound ubiquinol partially prevented the loss of mitochondrial respiratory function induced by peroxynitrite. These findings are analysed in terms of the redox transitions of ubiquinone linked to both nitrogen-centred radical scavenging and oxygen-centred radical production. It may be concluded that the reaction of mitochondrial ubiquinol with peroxynitrite is part of a complex regulatory mechanism with implications for mitochondrial function and integrity.
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July 2000
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Research Article|
June 26 2000
Oxidation of ubiquinol by peroxynitrite: implications for protection of mitochondria against nitrosative damage
Francisco SCHÖPFER;
Francisco SCHÖPFER
1
*Laboratory of Oxygen Metabolism, University Hospital, School of Medicine, University of Buenos Aires, Córdoba 2351, Buenos Aires, Argentina (1120)
1To whom correspondence should be addressed (e-mail fschopfer@;hotmail.com).
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Natalia RIOBÓ;
Natalia RIOBÓ
*Laboratory of Oxygen Metabolism, University Hospital, School of Medicine, University of Buenos Aires, Córdoba 2351, Buenos Aires, Argentina (1120)
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María Cecilia CARRERAS;
María Cecilia CARRERAS
*Laboratory of Oxygen Metabolism, University Hospital, School of Medicine, University of Buenos Aires, Córdoba 2351, Buenos Aires, Argentina (1120)
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Beatriz ALVAREZ;
Beatriz ALVAREZ
†Laboratory of Enzymology, School of Science, Universidad de la República, Montevideo, Uruguay
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Rafael RADI;
Rafael RADI
‡Department of Biochemistry and Laboratory of Free Radicals, School of Medicine, Universidad de la República, Montevideo, Uruguay
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Alberto BOVERIS;
Alberto BOVERIS
§Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina
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Enrique CADENAS;
Enrique CADENAS
¶Department of Molecular Pharmacology and Toxicology. School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089-9121, U.S.A.
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Juan José PODEROSO
Juan José PODEROSO
*Laboratory of Oxygen Metabolism, University Hospital, School of Medicine, University of Buenos Aires, Córdoba 2351, Buenos Aires, Argentina (1120)
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Biochem J (2000) 349 (1): 35–42.
Article history
Received:
January 17 2000
Revision Received:
March 30 2000
Accepted:
April 28 2000
Citation
Francisco SCHÖPFER, Natalia RIOBÓ, María Cecilia CARRERAS, Beatriz ALVAREZ, Rafael RADI, Alberto BOVERIS, Enrique CADENAS, Juan José PODEROSO; Oxidation of ubiquinol by peroxynitrite: implications for protection of mitochondria against nitrosative damage. Biochem J 1 July 2000; 349 (1): 35–42. doi: https://doi.org/10.1042/bj3490035
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