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Cationic uncouplers of oxidative phosphorylation are inducers of mitochondrial permeability transition
Author(s) -
Shinohara Yasuo,
Bandou Shidzuko,
Kora Shinichi,
Kitamura Seiichiro,
Inazumi Shuuji,
Terada Hiroshi
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)00499-2
Subject(s) - mitochondrial permeability transition pore , oxidative phosphorylation , mitochondrion , chemistry , biophysics , divalent , cationic polymerization , inner mitochondrial membrane , biochemistry , biology , organic chemistry , apoptosis , programmed cell death
To determine whether cationic uncouplers of oxidative phosphorylation induce permeability transition in mitochondria, the effects of the divalent cationic sulfhydryl cross‐linker copper‐ o ‐phenanthroline (Cu(OP) 2 ) and the cyanine dye tri‐S‐C 4 (5) on rat liver mitochondria were examined. Like Ca 2+ , they accelerated mitochondrial respiration with succinate and induced mitochondrial swelling when inorganic phosphate (Pi) was present in the incubation medium. The acceleration of respiration and swelling were inhibited by the SH‐reagent N ‐ethylmaleimide, and by the specific permeability transition inhibitor cyclosporin A (CsA). In addition, these cations, like Ca 2+ , induced release of ADP entrapped in the mitochondrial matrix space, and the morphological change of mitochondria induced by these cations was essentially the same as that induced by Ca 2+ . It is concluded that the uncoupling actions of Cu(OP) 2 and tri‐S‐C 4 (5) are due to induction of permeability transition in the inner mitochondrial membrane.