Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel

Date

2005-03-16

Authors

Dejean, Laurent M.
Martínez-Caballero, Sonia
Guo, Liang
Hughes, Cynthia
Ducret, Thomas
Ichas, François
Korsmeyer, Stanley J.
Antonsson, Bruno
Jonas, Elizabeth A.

Director

Publisher

American Society for Cell Biology
Acceso cerrado / Sarbide itxia
Artículo / Artikulua

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Abstract

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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Acceso cerrado a este documento. No se encuentra disponible para la consulta pública. Depositado en Academica-e para cumplir con los requisitos de evaluación y acreditación académica del autor/a (sexenios, acreditaciones, etc.).

Keywords

Department

Ciencias de la Salud / Osasun Zientziak

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item.page.cita

Dejean, L. M., Martinez-Caballero, S., Guo, L., Hughes, C., Teijido, O., Ducret, T., Ichas, F., Korsmeyer, S. J., Antonsson, B., Jonas, E. A., Kinnally, K. W. (2005) Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel. Molecular Biology of the Cell, 16(5), 2424-2432. https://doi.org/10.1091/mbc.e04-12-1111

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© 2005 by The American Society for Cell Biology

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