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COX5B Regulates MAVS-mediated Antiviral Signaling through Interaction with ATG5 and Repressing ROS Production
Open accessAbstract
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.
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“Multiple studies have demonstrated that mitochondrial fusion promotes, whereas mitochondrial fission inhibits RLR signaling (Castanier et al., 2010; Yasukawa et al., 2009; Zhao et al., 2012).”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Zhao et al., 2012
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Metadata
- Authors
- Zhao, Y., Sun, X., Nie, X., Sun, L., Tang, T.-S., Chen, D., & Sun, Q.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Sun, Qinmiao
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-12-20
- Volume
- 8
- Issue
- 12
- Pages
- e1003086
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC3534373
- OpenAlex
- W1974115318
- Cited by
- 129
- References
- 53
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 10 · 2022: 7 · 2021: 11 · 2020: 13 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 14 · 2015: 14 · 2014: 9 · 2013: 3
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Texas Southwestern Medical Center
- National Natural Science Foundation of China (2010CB945300)
- Chinese Academy of Sciences
- Tsinghua University
- Wuhan University
- National Key Research and Development Program of China (2010CB945300)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- COX5B, MAVS, cytochrome c oxidase, antiviral signaling, reactive oxygen species, autophagy, ATG5, mitochondria, antiviral innate immunity, autoimmunity
- MeSH terms
- Autophagy-Related Protein 5, Animals, Autophagy, Cells, Cultured, Electron Transport Complex IV, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunity, Innate, Microtubule-Associated Proteins, Mitochondria, Protein Binding, RNA, Messenger, Vesicular stomatitis Indiana virus, Virion, Blotting, Western, Signal Transduction, NF-kappa B, Apoptosis, Reactive Oxygen Species, Reverse Transcriptase Polymerase Chain Reaction, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Cell Proliferation, Vesicular Stomatitis, Real-Time Polymerase Chain Reaction
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