Oligomeric Bax Is a Component of the Putative CytochromecRelease Channel MAC, Mitochondrial Apoptosis-induced Channel

Molecular Biology of the Cell - Tập 16 Số 5 - Trang 2424-2432 - 2005
Laurent M. Dejean1, Sonia Martínez-Caballero2, Liang Guo2, Cynthia Hughes2, Oscar Teijido2, Thomas Ducret3, François Ichas3, Stanley J. Korsmeyer4, Bruno Antonsson5, Elizabeth A. Jonas6, Kathleen W. Kinnally2
1Department of Basic Sciences, College of Dentistry, New York University, New York, NY 10010, USA.
2Department of Basic Sciences, College of Dentistry, New York University, New York, NY 10010
3Institut National de la Santé et de la Recherche Médicale, Centre de Lutte Contre le Cancer Bergonié and Institut Européen de Chimie et Biologie, 33600 Pessac, France
4Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
5Serono Pharmaceutical Research Institute, Serono International S.A., Geneva, Switzerland
6Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520

Tóm tắt

Bcl-2 family proteins regulate apoptosis, in part, by controlling formation of the mitochondrial apoptosis-induced channel (MAC), which is a putative cytochrome c release channel induced early in the intrinsic apoptotic pathway. This channel activity was never observed in Bcl-2–overexpressing cells. Furthermore, MAC appears when Bax translocates to mitochondria and cytochrome c is released in cells dying by intrinsic apoptosis. Bax is a component of MAC of staurosporine-treated HeLa cells because MAC activity is immunodepleted by Bax antibodies. MAC is preferentially associated with oligomeric, not monomeric, Bax. The single channel behavior of recombinant oligomeric Bax and MAC is similar. Both channel activities are modified by cytochrome c, consistent with entrance of this protein into the pore. The mean conductance of patches of mitochondria isolated after green fluorescent protein-Bax translocation is significantly higher than those from untreated cells, consistent with onset of MAC activity. In contrast, the mean conductance of patches of mitochondria indicates MAC activity is present in apoptotic cells deficient in Bax but absent in apoptotic cells deficient in both Bax and Bak. These findings indicate Bax is a component of MAC in staurosporine-treated HeLa cells and suggest Bax and Bak are functionally redundant as components of MAC.

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Molecular Biology of the Cell

Tập 16 Số 5

2424-2432

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