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 apo...

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Bibliographic Details
Published in:The Journal of cell biology 2001-11, Vol.155 (5), p.725-731
Main Authors: Pavlov, Evgeny V., Priault, Muriel, Pietkiewicz, Dawn, Emily H.-Y. Cheng, Antonsson, Bruno, Manon, Stephen, Korsmeyer, Stanley J., Mannella, Carmen A., Kinnally, Kathleen W.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - physiology
Bax protein
bcl-2-Associated X Protein
Cell division
Cells
Cellular biology
Cellular immunity
Cytochromes
Electrophysiology
Humans
Intracellular Membranes - metabolism
Ion channels
Ion Channels - metabolism
Liposomes
Liposomes - chemistry
Liposomes - metabolism
Mitochondria
Mitochondria - metabolism
P branes
Patch-Clamp Techniques
Porins - metabolism
Proteolipids - chemistry
Proteolipids - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Voltage-Dependent Anion Channels
Yeast
Yeasts
Yeasts - physiology
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200107057