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 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.
Pavlov
E V
EV
Division of Basic Sciences, New York University College of Dentistry, New York, NY 10010, USA.
Priault
M
M
Pietkiewicz
D
D
Cheng
E H
EH
Antonsson
B
B
Manon
S
S
Korsmeyer
S J
SJ
Mannella
C A
CA
Kinnally
K W
KW
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018272:Porins / Q000378:metabolism; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels; D015003:Yeasts / Q000502:physiology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D007473:Ion Channels; D008081:Liposomes; D018272:Porins; D011510:Proteolipids; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; C020485:proteoliposomes