A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast

During apoptosis, proapoptotic factors are released from mitochondria by as yet undefined mechanisms. Patch-clamping of mitochondria and proteoliposom es formed from mitochondrial outer membranes of mammalian (FL5.12) cells ha s uncovered a novel ion channel whose activity correlates with onset of apo ptosis. The pore diameter inferred from the largest conductance state of th is channel is similar to4 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 pr operties. Thus, the channel activity correlates with presence of proapoptot ic Bax in the mitochondrial outer membrane and is absent in mitochondria fr om cells overexpressing antiapoptotic Bcl-2. Also, a similar channel activi ty is found in mitochondrial outer membranes of yeast expressing human Bax. These findings implicate this channel, named mitochondrial apoptosis-induc ed channel, as a candidate for the outer-membrane pore through which cytoch rome c and possibly other factors exit mitochondria during apoptosis.