Tom70 mediates activation of interferon regulatory factor 3 on mitochondria

	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.