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

Author

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  • Yuki Hanada

    (Graduate School of Science, Osaka University
    Graduate School of Medical Science, Kyushu University)

  • Naotada Ishihara

    (Graduate School of Science, Osaka University
    Institute of Life Science, Kurume University)

  • Lixiang Wang

    (Graduate School of Medical Science, Kyushu University
    Kurume University School of Medicine)

  • Hidenori Otera

    (Graduate School of Medical Science, Kyushu University)

  • Takaya Ishihara

    (Graduate School of Science, Osaka University)

  • Takumi Koshiba

    (Fukuoka University)

  • Katsuyoshi Mihara

    (Graduate School of Medical Science, Kyushu University)

  • Yoshihiro Ogawa

    (Graduate School of Medical Science, Kyushu University)

  • Masatoshi Nomura

    (Graduate School of Medical Science, Kyushu University
    Kurume University School of Medicine)

Abstract

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.

Suggested Citation

  • Yuki Hanada & Naotada Ishihara & Lixiang Wang & Hidenori Otera & Takaya Ishihara & Takumi Koshiba & Katsuyoshi Mihara & Yoshihiro Ogawa & Masatoshi Nomura, 2020. "MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19287-7
    DOI: 10.1038/s41467-020-19287-7
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    Cited by:

    1. William A. Hofstadter & Katelyn C. Cook & Elene Tsopurashvili & Robert Gebauer & Vojtěch Pražák & Emily A. Machala & Ji Woo Park & Kay Grünewald & Emmanuelle R. J. Quemin & Ileana M. Cristea, 2024. "Infection-induced peripheral mitochondria fission drives ER encapsulations and inter-mitochondria contacts that rescue bioenergetics," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

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