Article
- The EMBO Journal (2005) 24, 2096 - 2103
- doi:10.1038/sj.emboj.7600675
Published online: 26 May 2005
Subject Categories:
Bax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis
Matthew G Annis1, Erinn L Soucie2, Paulina J Dlugosz1, Jorge A Cruz-Aguado1, Linda Z Penn2, Brian Leber3 and David W Andrews1
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
- Ontario Cancer Institute, Toronto, Ontario, Canada
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Correspondence to:
David W Andrews, Department of Biochemistry, McMaster University, Health Sciences Center, 4H41B, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. Tel.: +1 905 525 9140 ext 22075; Fax: +1 905 522 9033; E-mail: andrewsd@mcmaster.ca
Received 21 October 2004; Accepted 15 April 2005
Abstract
Bax promotes cell death by permeabilizing mitochondrial outer membranes by an unresolved mechanism. However, in cells lacking the gene c-myc, membrane permeabilization by Bax is blocked by changes in the mitochondria that prevent Bax oligomerization. Drug-treated c-myc null cells and cells expressing Myc were used to map the topology of Bax in membranes prior to and after mitochondrial permeabilization. Chemical labeling of single cysteine mutants of Bax using a membrane bilayer impermeant cysteine-specific modifying agent revealed that Bax inserted both the 'pore domain' (helices 
5–6), and the tail-anchor (helix 9) into membranes prior to oligomerization and membrane permeabilization. Additional topology changes for Bax were not required in Myc-expressing cells to promote oligomerization and cytochrome c release. Our results suggest that unlike most pore-forming proteins, Bax membrane permeabilization results from oligomerization of transmembrane monomers rather than concerted insertion of the pore domains of a preformed oligomer.
Keywords:
- apoptosis,
- Bax,
- membrane topology,
- membrane permeabilization,
- Myc
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