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Opening of the mitochondrial permeability transition pore by uncoupling or inorganic phosphate in the presence of Ca 2+ is dependent on mitochondrial‐generated reactive oxygen species
Author(s) -
Kowaltowski Alicia J.,
Castilho Roger F.,
Vercesi Anibal E.
Publication year - 1996
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 - 10.1016/0014-5793(95)01449-7
Subject(s) - mitochondrial permeability transition pore , reactive oxygen species , phosphate , chemistry , permeability (electromagnetism) , oxygen , inorganic phosphate , biophysics , mitochondrial membrane transport protein , mitochondrion , inner mitochondrial membrane , biochemistry , biology , membrane , apoptosis , organic chemistry , programmed cell death
In this study, we show that mitochondrial membrane permeability transition in Ca 2+ ‐loaded mitochondria treated with carbonyl cyanide p ‐(trifluoromethoxy)phenylhydrazone (FCCP) or inorganic phosphate (P i ) is preceded by enhanced production of H 2 O 2 . This production is inhibited either by ethylene glycol‐bis( b ‐aminoethyl ether) N , N , N ′, N ′‐tetraacetic acid (EGTA) or Mg 2+ , but not by cyclosporin A. Permeability transition is prevented either by EGTA, catalase or dithiothreitol, suggesting the involvement of Ca 2+ , H 2 O 2 and oxidation of membrane protein thiols in this mechanism. When mitochondria are incubated under anaerobiosis, no permeabilization or H 2 O 2 production occurs. Based on these results we conclude that mitochondrial permeability transition induced by P i or FCCP‐uncoupling is dependent on mitochondrial‐generated reactive oxygen species.