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

Autor: Pavlov EV; Division of Basic Sciences, New York University College of Dentistry, New York, NY 10010, USA., Priault M, Pietkiewicz D, Cheng EH, Antonsson B, Manon S, Korsmeyer SJ, Mannella CA, Kinnally KW
Jazyk: angličtina
Zdroj: The Journal of cell biology [J Cell Biol] 2001 Nov 26; Vol. 155 (5), pp. 725-31. Date of Electronic Publication: 2001 Nov 26.
DOI: 10.1083/jcb.200107057
Abstrakt: 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 approximately 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.
Databáze: MEDLINE