Tom70 mediates activation of interferon regulatory factor 3 on mitochondria | |
Liu, XY; Wei, B; Shi, HX; Shan, YF; Wang, C | |
刊名 | CELL RESEARCH |
2010 | |
卷号 | 20期号:9页码:994-1011 |
关键词 | Tom70 MAVS IRF3 Hsp90 antiviral innate immunity |
通讯作者 | Wang, C (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China.,cwang01@sibs.ac.cn |
英文摘要 | Intracellular RNA viruses are sensed by receptors retinoic acid-inducible gene 1 (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) that trigger the formation of MAVS signal complex on mitochondria. Consequently, this leads to the activation of TANK-binding kinase 1 (TBK1) and phosphorylation of interferon regulatory factor 3 (IRF3), both of which constitutively associate with cytosolic chaperone Hsp90. It remains largely unknown how MAVS activates TBK1/IRF3. In this study, we identified translocases of outer membrane 70 (Tom70), a mitochondrial import receptor, to interact with MAVS upon RNA virus infection. Ectopic expression or knockdown of Tom70 could enhance or impair IRF3-mediated gene expression, respectively. Mechanistically, the clamp domain (R192) of Tom70 interacts with the C-terminal motif (EEVD) of Hsp90, thus recruiting TBK1/IRF3 to mitochondria. Disruption of this interaction or mislocation of Tom70 sharply impairs activation of TBK1 and IRF3. Furthermore, host antiviral responses are significantly boosted or crippled in the presence or absence of Tom70. Collectively, our study characterizes Tom70 as a critical adaptor linking MAVS to TBK1/IRF3, revealing that mitochondrion is evolutionarily integrated with innate immunity. |
学科主题 | Cell Biology |
类目[WOS] | Cell Biology |
关键词[WOS] | HEPATITIS-C VIRUS ; RIG-I ; ADAPTER PROTEIN ; ANTIVIRAL PATHWAY ; OUTER-MEMBRANE ; KAPPA-B ; MAVS ; IRF3 ; RECOGNITION ; RESPONSES |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000281483800006 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/1046] |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Liu, XY,Wei, B,Shi, HX,et al. Tom70 mediates activation of interferon regulatory factor 3 on mitochondria[J]. CELL RESEARCH,2010,20(9):994-1011. |
APA | Liu, XY,Wei, B,Shi, HX,Shan, YF,&Wang, C.(2010).Tom70 mediates activation of interferon regulatory factor 3 on mitochondria.CELL RESEARCH,20(9),994-1011. |
MLA | Liu, XY,et al."Tom70 mediates activation of interferon regulatory factor 3 on mitochondria".CELL RESEARCH 20.9(2010):994-1011. |
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