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

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Abstract

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. © 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

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Lim, M. L. R., Minamikawa, T., & Nagley, P. (2001). The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells. FEBS Letters, 503(1), 69–74. https://doi.org/10.1016/S0014-5793(01)02693-X

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