Mitofusin 2 inhibits mitochondrial antiviral signaling

Kai Yasukawa, Hiroyuki Oshiumi, Makoto Takeda, Naotada Ishihara, Yusuke Yanagi, Tsukasa Seya, Shun-Ichiro Kawabata, Takumi Koshiba

研究成果: ジャーナルへの寄稿記事

139 引用 (Scopus)

抄録

The innate immune response to viral infection involves the activation of multiple signaling steps that culminate in the production of type I interferons (IFNs). Mitochondrial antiviral signaling (MAVS), a mitochondrial outer membrane adaptor protein, plays an important role in this process. Here, we report that mitofusin 2 (Mfn2), a mediator of mitochondrial fusion, interacts with MAVS to modulate antiviral immunity. Overexpression of Mfn2 resulted in the inhibition of retinoic acid-inducible gene I (RIG-I) and melanoma differentiation- associated gene 5 (MDA-5), two cytosolic sensors of viral RNA, as well as of MAVS-mediated activation of the transcription factors interferon regulatory factor 3 (IRF-3) and nuclear factor κB (NF-κB). In contrast, loss of endogenous Mfn2 enhanced virus-induced production of IFN-β and thereby decreased viral replication. Structure-function analysis revealed that Mfn2 interacted with the carboxyl-terminal region of MAVS through a heptad repeat region, providing a structural perspective on the regulation of the mitochondrial antiviral response. Our results suggest that Mfn2 acts as an inhibitor of antiviral signaling, a function that may be distinct from its role in mitochondrial dynamics.

元の言語英語
ジャーナルScience Signaling
2
発行部数84
DOI
出版物ステータス出版済み - 8 18 2009

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Antiviral Agents
Mitochondrial Dynamics
Genes
Chemical activation
Interferon Regulatory Factor-3
Interferon Type I
Viral RNA
Virus Diseases
Tretinoin
Viruses
Innate Immunity
Interferons
Immunity
Melanoma
Membrane Proteins
Transcription Factors
Fusion reactions
Membranes
Sensors
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Yasukawa, K., Oshiumi, H., Takeda, M., Ishihara, N., Yanagi, Y., Seya, T., ... Koshiba, T. (2009). Mitofusin 2 inhibits mitochondrial antiviral signaling. Science Signaling, 2(84). https://doi.org/10.1126/scisignal.2000287

Mitofusin 2 inhibits mitochondrial antiviral signaling. / Yasukawa, Kai; Oshiumi, Hiroyuki; Takeda, Makoto; Ishihara, Naotada; Yanagi, Yusuke; Seya, Tsukasa; Kawabata, Shun-Ichiro; Koshiba, Takumi.

:: Science Signaling, 巻 2, 番号 84, 18.08.2009.

研究成果: ジャーナルへの寄稿記事

Yasukawa, K, Oshiumi, H, Takeda, M, Ishihara, N, Yanagi, Y, Seya, T, Kawabata, S-I & Koshiba, T 2009, 'Mitofusin 2 inhibits mitochondrial antiviral signaling', Science Signaling, 巻. 2, 番号 84. https://doi.org/10.1126/scisignal.2000287
Yasukawa K, Oshiumi H, Takeda M, Ishihara N, Yanagi Y, Seya T その他. Mitofusin 2 inhibits mitochondrial antiviral signaling. Science Signaling. 2009 8 18;2(84). https://doi.org/10.1126/scisignal.2000287
Yasukawa, Kai ; Oshiumi, Hiroyuki ; Takeda, Makoto ; Ishihara, Naotada ; Yanagi, Yusuke ; Seya, Tsukasa ; Kawabata, Shun-Ichiro ; Koshiba, Takumi. / Mitofusin 2 inhibits mitochondrial antiviral signaling. :: Science Signaling. 2009 ; 巻 2, 番号 84.
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