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The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells
Author(s) -
Lim Maria L.R,
Minamikawa Tetsuhiro,
Nagley Phillip
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02693-x
Subject(s) - protonophore , cytochrome c , apoptosome , mitochondrion , mitochondrial permeability transition pore , apoptosis , cytochrome , microbiology and biotechnology , mitochondrial apoptosis induced channel , staurosporine , programmed cell death , chemistry , cytochrome c oxidase , biology , biochemistry , biophysics , enzyme , phosphorylation , protein kinase c , caspase
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.