During apoptosis, proapoptotic factors are released from mitochondria by as yet undefined mechanisms. Patch-clamping of mitochondria and proteoliposomes formed from mitochondrial outer membranes of mammalian (FL5.12) cells has uncovered a novel ion channel whose activity correlates with onset of apoptosis. The pore diameter inferred from the largest conductance state of this channel is ∼4 nm, sufficient to allow diffusion of cytochrome c and even larger proteins. The activity of the channel is affected by Bcl-2 family proteins in a manner consistent with their pro- or antiapoptotic properties. Thus, the channel activity correlates with presence of proapoptotic Bax in the mitochondrial outer membrane and is absent in mitochondria from cells overexpressing antiapoptotic Bcl-2. Also, a similar channel activity is found in mitochondrial outer membranes of yeast expressing human Bax. These findings implicate this channel, named mitochondrial apoptosis–induced channel, as a candidate for the outer-membrane pore through which cytochrome c and possibly other factors exit mitochondria during apoptosis.
A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast
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Evgeny V. Pavlov, Muriel Priault, Dawn Pietkiewicz, Emily H.-Y. Cheng, Bruno Antonsson, Stephen Manon, Stanley J. Korsmeyer, Carmen A. Mannella, Kathleen W. Kinnally; A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast . J Cell Biol 26 November 2001; 155 (5): 725–732. doi: https://doi.org/10.1083/jcb.200107057
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