COX5B Regulates MAVS-mediated Antiviral Signaling through Interaction with ATG5 and Repressing ROS Production

PLoS Pathogens

Tie-shan Tang¹  Xuanli Nie¹  Xiaofeng Sun¹  Qinmiao Sun¹  Yuanyuan Zhao¹  Liwei Sun²  Dahua Chen² 

[1] State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing, P. R. China;State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing, P. R. China

关键词: Mitochondria;    Antiviral immune response;    Transfection;    RNA interference;    Autophagic cell death;    Hyperexpression techniques;    Sendai virus;    Redox signaling;   

DOI  :  10.1371/journal.ppat.1003086

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Innate antiviral immunity is the first line of the host defense system that rapidly detects invading viruses. Mitochondria function as platforms for innate antiviral signal transduction in mammals through the adaptor protein, MAVS. Excessive activation of MAVS-mediated antiviral signaling leads to dysfunction of mitochondria and cell apoptosis that likely causes the pathogenesis of autoimmunity. However, the mechanism of how MAVS is regulated at mitochondria remains unknown. Here we show that the Cytochrome c Oxidase (CcO) complex subunit COX5B physically interacts with MAVS and negatively regulates the MAVS-mediated antiviral pathway. Mechanistically, we find that while activation of MAVS leads to increased ROS production and COX5B expression, COX5B down-regulated MAVS signaling by repressing ROS production. Importantly, our study reveals that COX5B coordinates with the autophagy pathway to control MAVS aggregation, thereby balancing the antiviral signaling activity. Thus, our study provides novel insights into the link between mitochondrial electron transport system and the autophagy pathway in regulating innate antiviral immunity.

【 授权许可】

CC BY