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- Title
Mitofusin 2 Inhibits Mitochondrial Antiviral Signaling.
- Authors
Yasukawa, Kai; Oshiumi, Hiroyuki; Takeda, Makoto; Ishihara, Naotada; Yanagi, Yusuke; Seya, Tsukasa; Kawabata, Shun-ichiro; Koshiba, Takumi
- Abstract
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.
- Publication
Science Signaling, 2009, Vol 2, Issue 84, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.2000287