Active Bax and Bak are functional holins
Active Bax and Bak are functional holins
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DOI：
10.1101/gad.171645.111
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发表时间：
2011-11-01
影响因子：
10.5
通讯作者：
Luo, Xu
中科院分区：
文献类型：
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作者：
Pang, Xiaming;Moussa, Samir H.;Luo, Xu
Bax/Bak依赖的线粒体外膜透化（MOMP），主要由Bcl-2家族蛋白控制的中央凋亡事件的机制仍然没有得到很好的理解。在这里，我们表达活性Bax/巴克在细菌中，线粒体的假定起源，并检查其功能相似的λ噬菌体（λ）holin。作为细菌裂解的关键效应物，孔蛋白寡聚体形成膜损伤，通过膜损伤，内溶素（一种壁溶酶）在感染周期结束时逃离细胞质以攻击细胞壁。我们发现，活性Bax/巴克，而不是任何其他Bcl-2家族蛋白，显示holin行为，引起细菌裂解，通过释放内溶素在寡聚化依赖的方式。引人注目的是，用Bax/巴克的活性等位基因替换holin基因导致噬斑形成突变。此外，我们提供的证据表明，活性Bax产生大的膜孔，其大小是由Bax的结构元素控制。值得注意的是，通过活性Bax的裂解被Bcl-xL抑制，并且野生型Bax的裂解活性被仅BH 3蛋白刺激。总之，这些结果在机械上将MOMP与细菌质膜中的holin介导的孔形成联系起来。
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 lambda bacteriophage (lambda) 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.