Bax is a Bcl-2-family protein with pro-apoptotic activity that can form channels in lipid membranes. The protein has been shown to trigger cytochrome c release from mitochondria both in vitro and in vivo. Recombinant human Bax isolated in the presence of detergent was found to be present as an oligomer with an apparent molecular mass of approx. 160000 Da on gel filtration. When Bax was isolated in the absence of detergent the purified protein was monomeric with an apparent molecular mass of 22000 Da. Bax oligomers formed channels in liposomes and triggered cytochrome c release from isolated mitochondria, whereas monomeric Bax was inactive in both respects. Incubation of the monomeric Bax with 2% octyl glucoside induced formation of oligomers that displayed channel-forming activity in liposomes and triggered cytochrome c release from mitochondria. Triton X-100, Nonidet P-40 and n-dedecyl maltoside also activated monomeric Bax, whereas CHAPS had no activating effect. In cytosolic extracts from mouse liver, Bax migrated at a molecular mass of 24000 Da on gel filtration, whereas after incubation of the cytosol with 2% octyl glucoside Bax migrated at approximately 140000 Da. These results show that oligomeric Bax possesses channel-forming activity whereas monomeric Bax has no such activity.
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January 2000
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Research Article|
January 10 2000
Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria
Bruno ANTONSSON;
Bruno ANTONSSON
1
1To whom correspondence should be addressed (e-mail bruno.antonsson.ch-gva03@;serono.com).
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Sylvie MONTESSUIT;
Sylvie MONTESSUIT
1Serono Pharmaceutical Research Institute, Ares-Serono International S. A., 14, chemin des Aulx, CH-1228 Plan-les Ouates, Geneva, Switzerland
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Sandra LAUPER;
Sandra LAUPER
1Serono Pharmaceutical Research Institute, Ares-Serono International S. A., 14, chemin des Aulx, CH-1228 Plan-les Ouates, Geneva, Switzerland
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Robert ESKES;
Robert ESKES
1Serono Pharmaceutical Research Institute, Ares-Serono International S. A., 14, chemin des Aulx, CH-1228 Plan-les Ouates, Geneva, Switzerland
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Jean-Claude MARTINOU
Jean-Claude MARTINOU
1Serono Pharmaceutical Research Institute, Ares-Serono International S. A., 14, chemin des Aulx, CH-1228 Plan-les Ouates, Geneva, Switzerland
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Publisher: Portland Press Ltd
Received:
August 26 1999
Revision Received:
October 05 1999
Accepted:
October 29 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 345 (2): 271–278.
Article history
Received:
August 26 1999
Revision Received:
October 05 1999
Accepted:
October 29 1999
Citation
Bruno ANTONSSON, Sylvie MONTESSUIT, Sandra LAUPER, Robert ESKES, Jean-Claude MARTINOU; Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem J 15 January 2000; 345 (2): 271–278. doi: https://doi.org/10.1042/bj3450271
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