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Fatty acid‐induced uncoupling of oxidative phosphorylation is partly due to opening of the mitochondrial permeability transition pore
Author(s) -
Więckowski Mariusz R,
Wojtczak Lech
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00118-5
Subject(s) - protonophore , mitochondrial permeability transition pore , mitochondrion , oxidative phosphorylation , chemistry , biophysics , fatty acid , membrane potential , permeability (electromagnetism) , biochemistry , atp–adp translocase , inner mitochondrial membrane , membrane , biology , apoptosis , programmed cell death
Addition of myristate at low concentration (30–60 nmol/mg protein) to energized rat liver mitochondria resulted in dissipation of the electric membrane potential which, in Ca 2+ ‐free media, could be partly reversed by carboxyatractyloside but not by cyclosporin A. In contrast, in mitochondria preloaded with Ca 2+ this energy‐dissipating effect of fatty acid was partly prevented or reversed by cyclosporin A or ADP. In sucrose media, myristate, but not the protonophore carbonyl cyanide m ‐chlorophenylhydrazone, induced swelling of Ca 2+ ‐loaded mitochondria which was inhibited by cyclosporin A and ADP. We conclude that long‐chain fatty acids may induce opening of the mitochondrial permeability transition pore not only because of their protonophoric effect mediated by mitochondrial anion carriers [Skulachev, V.P., FEBS Lett. 294 (1991) 158–162; Więckowski, M.R. and Wojtczak, L., Biochem. Biophys. Res. Commun. (1997) 232, 414–417] but also by a direct interacton with the pore assembly.