Opening of the mitochondrial permeability transition pore by uncoupling or inorganic phosphate in the presence of Ca2+ is dependent on mitochondrial-generated reactive oxygen species
Opening of the mitochondrial permeability transition pore by uncoupling or inorganic phosphate in the presence of Ca2+ is dependent on mitochondrial-generated reactive oxygen species
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DOI：
10.1016/0014-5793(95)01449-7
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发表时间：
1996-01-08
期刊：
影响因子：
3.5
通讯作者：
Vercesi, AE
中科院分区：
文献类型：
--
作者：
Kowaltowski, AJ;Castilho, RF;Vercesi, AE
在这项研究中，我们发现，在含Ca2+的线粒体中，经过羰基氰化物对（三氟甲氧基）苯基腙（FCCP）或无机磷酸盐（p- i）处理的线粒体膜渗透性转变之前，H2O2的产生增强。乙二醇-双（b-氨基乙醚）N，N，N‘，N’-四乙酸（EGTA）或Mg2+均能抑制线粒体的通透性转变，而环孢素A则不能。EGTA、过氧化氢酶或二硫代苏糖醇均能阻止细胞膜的通透性转变，这表明Ca2+、H2O2和膜蛋白硫醇的氧化参与了这一机制。基于这些结果，我们得出结论，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。
In this study, we show that mitochondrial membrane permeability transition in Ca2+-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 glycol-bis(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.