2. Academic Validation
  3. Tom70 mediates Sendai virus-induced apoptosis on mitochondria

Tom70 mediates Sendai virus-induced apoptosis on mitochondria

  • J Virol. 2015 Apr;89(7):3804-18. doi: 10.1128/JVI.02959-14.
Bo Wei 1,  Ye Cui 1,  Yuefeng Huang 1,  Heng Liu 1,  Lin Li 1,  Mi Li 2,  Kang-Cheng Ruan 1,  Qin Zhou 3,  Chen Wang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 2 The Division of Molecular Nephrology and the Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
  • 3 The Division of Molecular Nephrology and the Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, Chongqing, China zhouqin@cqmu.edu.cn cwang01@sibcb.ac.cn.
  • 4 State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China zhouqin@cqmu.edu.cn cwang01@sibcb.ac.cn.
PMID: 25609812 DOI: 10.1128/JVI.02959-14
Abstract

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.

Importance: Apoptosis 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.

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