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Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway
Open accessAbstract
The intracellular retinoic acid-inducible gene I-like receptors (RLRs) sense viral ribonucleic acid and signal through the mitochondrial protein mitochondrial antiviral signalling (MAVS) to trigger the production of type I interferons and proinflammatory cytokines. In this study, we report that RLR activation promotes elongation of the mitochondrial network. Mimicking this elongation enhances signalling downstream from MAVS and favours the binding of MAVS to stimulator of interferon genes, an endoplasmic reticulum (ER) protein involved in the RLR pathway. By contrast, enforced mitochondrial fragmentation dampens signalling and reduces the association between both proteins. Our finding that MAVS is associated with a pool of mitofusin 1, a protein of the mitochondrial fusion machinery, suggests that MAVS is capable of regulating mitochondrial dynamics to facilitate the mitochondria-ER association required for signal transduction. Importantly, we observed that viral mitochondria-localized inhibitor of apoptosis, a cytomegalovirus (CMV) antiapoptotic protein that promotes mitochondrial fragmentation, inhibits signalling downstream from MAVS, suggesting a possible new immune modulation strategy of the CMV.
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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 Castanier et al., 2010
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Metadata
- Authors
- Castanier, C., Garcin, D., Vazquez, A., & Arnoult, D.
- Affiliations
- Université Paris-Sud (FR)
- University of Geneva (CH)
- Corresponding author
- Arnoult, Damien
- Venue
- The EMBO Reports
- Published
- 2009-12-18
- Volume
- 11
- Issue
- 2
- Pages
- 133-138
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC2828750
- OpenAlex
- W1993205112
- Cited by
- 316
- References
- 17
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 14 · 2023: 20 · 2022: 19 · 2021: 26 · 2020: 27 · 2019: 23 · 2018: 19 · 2017: 20 · 2016: 16 · 2015: 17 · 2014: 22 · 2013: 11 · 2012: 20
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- 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 › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial dynamics, RIG-I-like receptors, MAVS, mitochondrial fusion, mitofusin 1, mitochondrial fragmentation, STING, type I interferon signaling, viral RNA sensing, cytomegalovirus, immune evasion, antiviral innate immunity
- MeSH terms
- STING Protein, Antiviral Agents, Cells, Cultured, HeLa Cells, Humans, Immunity, Innate, Membrane Proteins, Mitochondria, Protein Binding, Virus Diseases, Signal Transduction, Receptors, Retinoic Acid, Mitochondrial Proteins, Organelle Shape, Organelle Size
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