Peroxynitrite and Brain Mitochondria: Evidence for Increased Proton Leak
作者： Paul S. Brookes , John M. Land , John B. Clark , Simon J. R. Heales
DOI: 10.1046/J.1471-4159.1998.70052195.X
关键词: Biophysics 、 Respiratory chain 、 Mitochondrial respiratory chain 、 Peroxynitrite 、 Lipid peroxidation 、 Biochemistry 、 Mitochondrial permeability transition pore 、 Cellular respiration 、 Inner mitochondrial membrane 、 Mitochondrion 、 Biology 、 Cellular and Molecular Neuroscience
摘要: Peroxynitrite has been reported to inhibit irreversibly mitochondrial respiration. Here we show that three sequential additions of 200 microM peroxynitrite (initial concentration) rat brain mitochondria (0.2 mg protein/ml) significantly stimulated state 4 respiration and further progressively inhibited it. No stimulation 3 or the maximal enzymatic activities respiratory chain complexes was observed on identical exposure. State is a consequence proton permeability inner membrane, demonstrate peroxynitrite-induced accompanied by decreased membrane potential, suggesting an increase in this leak. Cyclosporin A did not affect stimulation, no involvement transition pore. The prevented lipid-soluble vitamin E analogue Trolox, lipid peroxidation, proposed mechanism cytotoxicity. Lipid peroxidation previously bilayer permeability. high polyunsaturate content phospholipids may predispose them thus peroxynitrite-induced, peroxidation-mediated leak apply particularly certain neurodegenerative disorders thought proceed via mechanisms oxidative damage.
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