Tom70 Mediates Sendai Virus-Induced Apoptosis on Mitochondria
Tom70 Mediates Sendai Virus-Induced Apoptosis on Mitochondria
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DOI：
10.1128/jvi.02959-14
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发表时间：
2015-04-01
影响因子：
5.4
通讯作者：
Wang, Chen
中科院分区：
文献类型：
--
作者：
Wei, Bo;Cui, Ye;Wang, Chen
病毒感染立即引发先天免疫反应。除了宿主细胞因子和趋化因子的稳健表达外，细胞凋亡是限制病毒入侵的另一种有效手段。IRF 3最近被证明是仙台病毒（SeV）诱导的细胞凋亡必不可少的，但其潜在的机制还没有完全了解。在这里，我们报告了一个动态的蛋白质复合物，Tom 70/Hsp 90/IRF 3/Bax，介导SeV诱导的细胞凋亡。细胞溶质促凋亡蛋白Bax在病毒感染后与IRF 3特异性相互作用。线粒体外膜蛋白Tom 70通过Hsp 90将IRF 3募集到线粒体。因此，Bax重新定位到线粒体上诱导细胞色素c泄漏到胞质溶胶中并启动相应的凋亡。有趣的是，IKK-i是这种凋亡所必需的，而TBK 1是凋亡必需的。总的来说，我们的研究表征了一种新的蛋白质复合物，是重要的SeV诱导的apoptosis.IMPORTANCEApoptosis是一种有效的手段，牺牲病毒感染的细胞和抑制病毒的传播。在这项研究中，我们证明了IRF 3与Bax相关的病毒感染。Tom 70通过Hsp 90将该蛋白复合物募集到线粒体外膜，从而诱导细胞色素c释放到细胞质中，启动病毒诱导的细胞凋亡。有趣的是，IKK-i在这种激活中起着至关重要的作用。本研究揭示了SeV诱导细胞凋亡的新机制。
Virus infection triggers immediate innate immune responses. Apoptosis represents another effective means to restrict virus invasion, besides robust expression of host cytokines and chemokines. IRF3 was recently demonstrated to be indispensable for Sendai virus (SeV)-induced apoptosis, but the underlying mechanism is not fully understood. Here we report that a dynamic protein complex, Tom70/Hsp90/IRF3/Bax, mediates SeV-induced apoptosis. The cytosolic proapoptotic protein Bax interacts specifically with IRF3 upon virus infection. The mitochondrial outer membrane protein Tom70 recruits IRF3 to mitochondria via Hsp90. Consequently, the relocation of Bax onto mitochondria induces the leakage of cytochrome c into the cytosol and initiates the corresponding apoptosis. Interestingly, IKK-i is essential for this apoptosis, whereas TBK1 is dispensable. Collectively, our study characterizes a novel protein complex that is important for SeV-induced apoptosis.IMPORTANCEApoptosis is an effective means of sacrificing virus-infected cells and restraining the spread of virus. In this study, we demonstrate that IRF3 associates with Bax upon virus infection. Tom70 recruits this protein complex to the mitochondrial outer membrane through Hsp90, which thus induces the release of cytochrome c into the cytosol, initiating virus-induced apoptosis. Interestingly, IKK-i plays an essential role in this activation. This study uncovers a novel mechanism of SeV-induced apoptosis.