The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells
The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells
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DOI：
10.1016/s0014-5793(01)02693-x
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发表时间：
2001-08-10
期刊：
影响因子：
3.5
通讯作者：
Nagley, P
中科院分区：
文献类型：
--
作者：
Lim, MLR;Minamikawa, T;Nagley, P
线粒体通透性转换（MPT）和细胞色素c从线粒体的重新分配是与细胞凋亡相关的两个事件。我们研究了MPT事件是否强制性地导致细胞色素c在体内释放。我们以前已经表明，与质子载体间氯苯腙（CCCP）的人骨肉瘤细胞治疗6小时诱导MPT和线粒体肿胀，而没有显着的细胞死亡。在这里，我们证明了细胞色素c的释放不会发生，即使在用CCCP处理72小时后，细胞仍保持活力。Bax在这些条件下不被动员到线粒体。然而，随后暴露CCCP处理的细胞依托泊苷或星形孢菌素48小时的结果在快速细胞死亡和细胞色素c的释放，伴随着Bax与线粒体的关联，证明这些线粒体的能力，释放细胞色素c与额外的触发器。我们的研究结果表明，MPT本身并不是影响细胞色素c释放的充分条件。((C)2001年欧洲生物化学学会联合会。出版社：Elsevier Science B.V. All rights reserved.
Mitochondrial permeability transition (MPT) and cytochrome c redistribution from mitochondria are two events associated with apoptosis. We investigated whether an MPT event obligatorily leads to cytochrome c release in vivo. We have previously shown that treatment of human osteosarcoma cells with the protonophore m-chlorophenylhydrazone (CCCP) for 6 h induces MPT and mitochondrial swelling without significant cell death. Here we demonstrate that release of cytochrome c does not occur and the cells remain viable even after 72 h of treatment with CCCP. Bax is not mobilized to mitochondria under these conditions. However, subsequent exposure of CCCP-treated cells to etoposide or staurosporine for 48 h results in rapid cell death and cytochrome c release that is accompanied by Bax association with mitochondria, demonstrating competency of these mitochondria to release cytochrome c with additional triggers. Our findings suggest that MPT is not a sufficient condition, in itself, to effect cytochrome c release. ((C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V.. All rights reserved.