Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated membrane fluidity
Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated membrane fluidity
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DOI：
10.1016/s0014-5793(04)00071-7
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发表时间：
2004-02-27
期刊：
影响因子：
3.5
通讯作者：
Fernández-Checa, JC
中科院分区：
文献类型：
--
作者：
Colell, A;García-Ruiz, C;Fernández-Checa, JC
大鼠肝脏线粒体（CHM）的胆固醇富集可损害苍术苷诱导的线粒体通透性转变（MPT），这是由于膜流动性降低所致。在本研究中，我们探讨了胆固醇富集对活性氧（ROS）诱导的MPT的影响。黄嘌呤加黄嘌呤氧化酶产生的超氧阴离子引起CHM线粒体肿胀和细胞色素c释放，而丁基羟基甲苯、抗电压依赖性阴离子通道抗体或环孢素a可以阻止这一现象。在对照线粒体和CHM中，神经节苷脂GD3和线粒体GSH耗竭联合产生的过氧化氢引起线粒体肿胀和细胞色素c、Smac/Diablo和凋亡诱导因子的释放。因此，ROS诱导MPT和凋亡激活，而不考虑胆固醇富集导致的线粒体膜动力学降低。(C) 2004年欧洲生化学会联合会。Elsevier B.V.版权所有。
Cholesterol enrichment of rat liver mitochondria (CHM) impairs atractyloside-induced mitochondrial permeability transition (MPT) due to decreased membrane fluidity. In this study we addressed the effect of cholesterol enrichment on MPT induced by reactive oxygen species (ROS). Superoxide anion generated by xanthine plus xanthine oxidase triggered mitochondrial swelling and cytochrome c release in CHM, which was prevented by butylated hydroxytoluene, an anti-voltage-depenent anion channel antibody, or cyclosporin A. Furthermore, hydrogen peroxide generated by the combination of ganglioside GD3 and mitochondrial GSH depletion elicited mitochondrial swelling and release of cytochrome c, Smac/Diablo and apoptosis-inducing factor in control mitochondria and CHM. Thus, ROS induce MPT and apoptosome activation regardless of decreased mitochondrial membrane dynamics due to cholesterol enrichment. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.