TY - JOUR
T1 - MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity
AU - Hanada, Yuki
AU - Ishihara, Naotada
AU - Wang, Lixiang
AU - Otera, Hidenori
AU - Ishihara, Takaya
AU - Koshiba, Takumi
AU - Mihara, Katsuyoshi
AU - Ogawa, Yoshihiro
AU - Nomura, Masatoshi
N1 - Funding Information:
We thank Dr. Hiroki Kato and Dr. Keiji Masuda (Kyushu University) for supporting a generation of Mff-deficient cells and Dr. Mitsuhiro Nishigori (Fukuoka University) for supporting a virus infection experiment. We also thank all members of Professor Nomura’s (Kyushu University and Kurume University), Professor Ishihara’s (Osaka University), and Professor Ogawa’s (Kyushu University) laboratories for helpful discussions. We also thank the Research Support Center, Graduate School of Medical Science, Kyushu University for technical support. This work was supported by AMED-CREST (to N.I., under Grant Numbers JP20gm1110006 and JP20gm0810009), MEXT-Supported Program for the Strategic Research Foundation at Private Universities to Kurume University, by the Japanese Society for the Promotion of Science KAKENHI (to M.N., Grant Number 17K09885; to L.W., Grant Number 16K19557; to N.I., Grant Number 17H03677), and by Robert T. Huang Entrepreneurship Center of Kyushu University (QREC) Academic Challenge 2017 grants-in-aid for scientific research (to Y.H.). This paper is dedicated to the memory of Hidenori Otera, our dear friend and colleague, who passed away on 19th Oct 2019.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-020-19287-7
DO - 10.1038/s41467-020-19287-7
M3 - Article
C2 - 33177519
AN - SCOPUS:85095840392
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5711
ER -