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Sci. Signal., 1 February 2011
Vol. 4, Issue 158, p. ra7
[DOI: 10.1126/scisignal.2001147]

RESEARCH ARTICLES

Mitochondrial Membrane Potential Is Required for MAVS-Mediated Antiviral Signaling

Takumi Koshiba1*, Kai Yasukawa1, Yusuke Yanagi2, and Shun-ichiro Kawabata1

1 Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
2 Department of Virology, Faculty of Medicine, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

Abstract: Mitochondria, dynamic organelles that undergo cycles of fusion and fission, are the powerhouses of eukaryotic cells and are also involved in cellular innate antiviral immunity in mammals. Mitochondrial antiviral immunity depends on activation of the cytoplasmic retinoic acid–inducible gene I (RIG-I)–like receptor (RLR) signaling pathway and the participation of a mitochondrial outer membrane adaptor protein called MAVS (mitochondrial antiviral signaling). We found that cells that lack the ability to undergo mitochondrial fusion as a result of targeted deletion of both mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) exhibited impaired induction of interferons and proinflammatory cytokines in response to viral infection, resulting in increased viral replication. In contrast, cells with null mutations in either Mfn1 or Mfn2 retained their RLR-induced antiviral responses. We also found that a reduced mitochondrial membrane potential ({Delta}{Psi}m) correlated with the reduced antiviral response. The dissipation in {Delta}{Psi}m did not affect the activation of the transcription factor interferon regulatory factor 3 downstream of MAVS, which suggests that {Delta}{Psi}m and MAVS are coupled at the same stage in the RLR signaling pathway. Our results provide evidence that the physiological function of mitochondria plays a key role in innate antiviral immunity.

* To whom correspondence should be addressed. E-mail: koshiba{at}kyudai.jp

Citation: T. Koshiba, K. Yasukawa, Y. Yanagi, S.-i. Kawabata, Mitochondrial Membrane Potential Is Required for MAVS-Mediated Antiviral Signaling. Sci. Signal. 4, ra7 (2011).

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