Cationic uncouplers of oxidative phosphorylation are inducers of mitochondrial permeability transition

FEBS Letters

Shinohara, Yasuo¹  Terada, Hiroshi¹  Bandou, Shidzuko¹  Kitamura, Seiichiro²  Kora, Shinichi¹  Inazumi, Shuuji² 

[1]Faculty of Pharmaceutical Sciences, The University of Tokushima, Shomachi-1, Tokushima 770-8505, Japan

[2]Department of Anatomy, School of Dentistry, The University of Tokushima, Kuramotocho-3, Tokushima 770-8504, Japan

关键词: Uncoupler;    Permeability transition;    Ca2+;    Oxidative phosphorylation;    Liver mitochondrion;    Rat;    Tri-S-C4(5);    2;    2′-[3-[2-(3-butyl-4-methyl-2-thiazolin-2-ylidene) ethylidene] propenylene]-bis[3-butyl-4-methyl thiazolinium iodide];    Tri-S-C7(5);    2;    2′-[3-[2-(3-heptyl-4-methyl-2-thiazolin-2-ylidene)ethylidene]propenylene]-bis[3-heptyl-4-methyl thiazolinium iodide];    Cu(OP)2;    complex of copper with o-phenanthroline;    CsA;    cyclosporin A;    NEM;    N-ethylmaleimide;    TEM;    transmission electron microscopy;    Pi;    inorganic phosphate;   

DOI  :  10.1016/S0014-5793(98)00499-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-C₄(5) on rat liver mitochondria were examined. Like Ca²⁺, 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 Ca²⁺, 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 Ca²⁺. It is concluded that the uncoupling actions of Cu(OP)₂ and tri-S-C₄(5) are due to induction of permeability transition in the inner mitochondrial membrane.

【 授权许可】

Unknown