title: COX5B regulates MAVS-mediated antiviral signaling through interaction with ATG5 and repressing ROS production.
abstract: 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.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing, P.R. China.
authors: Yuanyuan
authors: Y
authors: Zhao
authors: Xiaofeng
authors: X
authors: Sun
authors: Xuanli
authors: X
authors: Nie
authors: Liwei
authors: L
authors: Sun
authors: Tie-Shan
authors: TS
authors: Tang
authors: Dahua
authors: D
authors: Chen
authors: Qinmiao
authors: Q
authors: Sun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D054243:Vesicular Stomatitis / Q000235:genetics / Q000276:immunology / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014771:Virion / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000071187:Autophagy-Related Protein 5; C505371:MAVS protein, human; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C480024:COX5B protein, human; D003576:Electron Transport Complex IV