Active Bax and Bak are functional holins

Xiaming Pang, Samir H. Moussa, Natalie M. Targy, Jeffrey L. Bose, Nicholas M. George, Casey Gries, Hernando Lopez, Liqiang Zhang, Kenneth W. Bayles, Ry Young, Xu Luo

Research output: Contribution to journalArticle

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 l bacteriophage (l) 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.

Original languageEnglish (US)
Pages (from-to)2278-2290
Number of pages13
JournalGenes and Development
Volume25
Issue number21
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Keywords

  • Bacterial lysis
  • Bacterial plasma membrane holes
  • Bacteriophage
  • Bax and bak
  • Holin
  • Mitochondrial outer membrane permeabilization (MOMP)

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Pang, X., Moussa, S. H., Targy, N. M., Bose, J. L., George, N. M., Gries, C., Lopez, H., Zhang, L., Bayles, K. W., Young, R., & Luo, X. (2011). Active Bax and Bak are functional holins. Genes and Development, 25(21), 2278-2290. https://doi.org/10.1101/gad.171645.111