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Publication : MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity.

First Author  Hanada Y Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  5711
PubMed ID  33177519 Mgi Jnum  J:297778
Mgi Id  MGI:6479256 Doi  10.1038/s41467-020-19287-7
Citation  Hanada Y, et al. (2020) MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity. Nat Commun 11(1):5711
abstractText  Mitochondria are multifunctional organelles that produce energy and are critical for various signaling pathways. Mitochondrial antiviral signaling (MAVS) is a mitochondrial outer membrane protein essential for the anti-RNA viral immune response, which is regulated by mitochondrial dynamics and energetics; however, the molecular link between mitochondrial metabolism and immunity is unclear. Here we show in cultured mammalian cells that MAVS is activated by mitochondrial fission factor (Mff), which senses mitochondrial energy status. Mff mediates the formation of active MAVS clusters on mitochondria, independent of mitochondrial fission and dynamin-related protein 1. Under mitochondrial dysfunction, Mff is phosphorylated by the cellular energy sensor AMP-activated protein kinase (AMPK), leading to the disorganization of MAVS clusters and repression of the acute antiviral response. Mff also contributes to immune tolerance during chronic infection by disrupting the mitochondrial MAVS clusters. Taken together, Mff has a critical function in MAVS-mediated innate immunity, by sensing mitochondrial energy metabolism via AMPK signaling.
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