Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway.
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.
Castanier
Céline
C
INSERM U542, Hôpital Paul Brousse, Bâtiment Lavoisier, Université Paris-Sud, 14 Avenue Paul Vaillant Couturier, Villejuif Cedex 94807, France.
Garcin
Dominique
D
Vazquez
Aimé
A
Arnoult
Damien
D
D000998:Antiviral Agents / Q000378:metabolism*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D053140:Organelle Shape / Q000276:immunology; D053141:Organelle Size / Q000276:immunology; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism; D000099197:STING Protein
D000998:Antiviral Agents; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018168:Receptors, Retinoic Acid; C532857:STING1 protein, human; D000099197:STING Protein