The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells

FEBS Letters

Minamikawa, Tetsuhiro¹  Nagley, Phillip¹  Lim, Maria L.R¹ 

[1] Department of Biochemistry and Molecular Biology, P.O. Box 13D, Monash University, Clayton, Vic. 3800, Australia

关键词: Mitochondrial permeability transition;    Cytochrome c;    Bax;    Cell death;    Mitochondrion;   

DOI  :  10.1016/S0014-5793(01)02693-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown