Kowaltowski A J, Castilho R F, Vercesi A E
Departamento de Bioquimica, I.B., UNICAMP, Campinas, SP, Brasil.
FEBS Lett. 1996 Jan 8;378(2):150-2. doi: 10.1016/0014-5793(95)01449-7.
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 H2O2. This production is inhibited either by ethylene glycobis(b-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) or Mg2+, but not by cyclosporin A. Permeability transition is prevented either by EGTA, catalase or dithiothreitol, suggesting the involvement of Ca2+, H2O2 and oxidation of membrane protein thiols in this mechanism. When mitochondria are incubated under anaerobiosis, no permeabilization or H2O2 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.
在本研究中，我们发现，在用羰基氰化物对（三氟甲氧基）苯腙（FCCP）或无机磷酸盐（P(i)）处理的钙负载线粒体中，线粒体膜通透性转变之前会出现过氧化氢生成增加。这种生成可被乙二醇双（β-氨基乙醚）N,N,N',N'-四乙酸（EGTA）或镁离子抑制，但不能被环孢素A抑制。EGTA、过氧化氢酶或二硫苏糖醇均可防止通透性转变，这表明该机制涉及钙离子、过氧化氢和膜蛋白硫醇的氧化。当线粒体在厌氧条件下孵育时，不会发生通透性改变或过氧化氢生成。基于这些结果，我们得出结论，由P(i)或FCCP解偶联诱导的线粒体通透性转变依赖于线粒体产生的活性氧。
