TY - JOUR
T1 - Active Bax and Bak are functional holins
AU - Pang, Xiaming
AU - Moussa, Samir H.
AU - Targy, Natalie M.
AU - Bose, Jeffrey L.
AU - George, Nicholas M.
AU - Gries, Casey
AU - Lopez, Hernando
AU - Zhang, Liqiang
AU - Bayles, Kenneth W.
AU - Young, Ry
AU - Luo, Xu
PY - 2011/11/1
Y1 - 2011/11/1
N2 - 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.
AB - 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.
KW - Bacterial lysis
KW - Bacterial plasma membrane holes
KW - Bacteriophage
KW - Bax and bak
KW - Holin
KW - Mitochondrial outer membrane permeabilization (MOMP)
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U2 - 10.1101/gad.171645.111
DO - 10.1101/gad.171645.111
M3 - Article
C2 - 22006182
AN - SCOPUS:80455140223
SN - 0890-9369
VL - 25
SP - 2278
EP - 2290
JO - Genes and Development
JF - Genes and Development
IS - 21
ER -