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

Yuki Hanada, Naotada Ishihara, Lixiang Wang, Hidenori Otera, Takaya Ishihara, Takumi Koshiba, Katsuyoshi Mihara, Yoshihiro Ogawa, Masatoshi Nomura

Nature communications 2020 Nov 11

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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.

Citation

Yuki Hanada, Naotada Ishihara, Lixiang Wang, Hidenori Otera, Takaya Ishihara, Takumi Koshiba, Katsuyoshi Mihara, Yoshihiro Ogawa, Masatoshi Nomura. MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity. Nature communications. 2020 Nov 11;11(1):5711