Volume 20, No 9, Sep 2010

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 20 Issue 9, September 2010: 994-1011

ORIGINAL ARTICLES

Tom70 mediates activation of interferon regulatory factor 3 on mitochondria

Xin-Yi Liu*, Bo Wei*, He-Xin Shi, Yu-Fei Shan and Chen Wang

Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Correspondence: Chen Wang,(cwang01@sibs.ac.cn)

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.

Cell Research (2010) 20:994-1011. doi: 10.1038/cr.2010.103; published online 13 July 2010

FULL TEXT | PDF

Browse 2182