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EMBO Rep. 2010 Feb;11(2):133-8. doi: 10.1038/embor.2009.258. Epub 2009 Dec 18.

Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway.

Author information

1
INSERM U542, Hôpital Paul Brousse, Bâtiment Lavoisier, Université Paris-Sud, 14 Avenue Paul Vaillant Couturier, Villejuif Cedex 94807, France.

Abstract

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.

PMID:
20019757
PMCID:
PMC2828750
DOI:
10.1038/embor.2009.258
[Indexed for MEDLINE]
Free PMC Article

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