Active Bax and Bak are functional holins
- Xiaming Pang1,
- Samir H. Moussa3,4,
- Natalie M. Targy1,4,
- Jeffrey L. Bose2,
- Nicholas M. George1,
- Casey Gries2,
- Hernando Lopez1,
- Liqiang Zhang1,
- Kenneth W. Bayles2,
- Ry Young3 and
- Xu Luo1,5
- 1Eppley Institute for Research in Cancer and Allied Diseases, and
- 2Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA;
- 3Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA
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↵4 These authors contributed equally to this work.
Abstract
The mechanism of Bax/Bak-dependent mitochondrial outer membrane permeabilization (MOMP), a central apoptotic event primarily controlled by the Bcl-2 family proteins, remains not well understood. Here, we express active Bax/Bak in bacteria, the putative origin of mitochondria, and examine their functional similarities to the λ bacteriophage (λ) holin. As critical effectors for bacterial lysis, holin oligomers form membrane lesions, through which endolysin, a muralytic enzyme, escapes the cytoplasm to attack the cell wall at the end of the infection cycle. We found that active Bax/Bak, but not any other Bcl-2 family protein, displays holin behavior, causing bacterial lysis by releasing endolysin in an oligomerization-dependent manner. Strikingly, replacing the holin gene with active alleles of Bax/Bak results in plaque-forming phages. Furthermore, we provide evidence that active Bax produces large membrane holes, the size of which is controlled by structural elements of Bax. Notably, lysis by active Bax is inhibited by Bcl-xL, and the lysis activity of the wild-type Bax is stimulated by a BH3-only protein. Together, these results mechanistically link MOMP to holin-mediated hole formation in the bacterial plasma membrane.
Keywords
- mitochondrial outer membrane permeabilization (MOMP)
- Bax and Bak
- holin
- bacteriophage
- bacterial plasma membrane holes
- bacterial lysis
Footnotes
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↵5 Corresponding author.
E-mail xuluo{at}unmc.edu.
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.171645.111.
- Received June 5, 2011.
- Accepted September 19, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press