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Type: Artigo de periódico
Title: 4,6-dinitro-o-cresol uncouples oxidative phosphorylation and induces membrane permeability transition in rat liver mitochondria
Author: Castilho, RF
Vicente, JAF
Kowaltowski, AJ
Vercesi, AE
Abstract: The effect of the herbicide 4,6-dinitro-o-cresol (DNOC), a structural analogue of the classical protonophore 2,4-dinitrophenol, on the bioenergetics and inner membrane permeability of isolated rat liver mitochondria was studied. We observed that DNOC (10-50 mu M) acts as a classical uncoupler of oxidative phosphorylation in rat liver mitochondria, promoting both an increase in succinate-supported mitochondrial respiration in the presence or absence of ADP and a decrease in transmembrane potential. The protonophoric activity of DNOC was evidenced by the induction of mitochondrial swelling: in hyposmotic Kf-acetate medium, in the presence of valinomycin. At higher concentrations (> 50 mu M), DNOC also induces an inhibition of succinate-supported respiration, and a decrease in the activity of the succinate dehydrogenase can be observed. The addition of uncoupling concentrations of DNOC to Ca2+-loaded mitochondria treated with Ruthenium Red results in non-specific membrane permeabilization, as evidenced by mitochondrial swelling in isosmotic sucrose medium. Cyclosporin A, which inhibits mitochondrial permeability transition, prevented DNOC-induced mitochondrial swelling in the presence of Ca2+, which was accompanied by a decrease in mitochondrial membrane protein thiol content, owing to protein thiol oxidation. Catalase partially inhibits mitochondrial swelling and protein thiol oxidation, indicating the participation of mitochondrial-generated reactive oxygen species in this process. It is concluded that DNOC is a potent protonophore acting as a classical uncoupler of oxidative phosphorylation in rat liver mitochondria by dissipating the proton electrochemical gradient. Treatment of Ca2+-loaded mitochondria with uncoupling concentrations of DNOC results in mitochondrial permeability transition, associated with membrane protein thiol oxidation by reactive oxygen species. Copyright (C) 1997 Elsevier Science Ltd.
Subject: calcium ion
cyclosporin A
mitochondrial respiration
mitochondrial permeability transition
Country: Inglaterra
Editor: Pergamon-elsevier Science Ltd
Citation: International Journal Of Biochemistry & Cell Biology. Pergamon-elsevier Science Ltd, v. 29, n. 7, n. 1005, n. 1011, 1997.
Rights: fechado
Identifier DOI: 10.1016/S1357-2725(97)00041-1
Date Issue: 1997
Appears in Collections:Unicamp - Artigos e Outros Documentos

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