Peroxisomes Are Signaling Platforms for Antiviral Innate Immunity

Dixit, E., Boulant, S., Zhang, Y., Lee, A. S., Odendall, C., Shum, B., Hacohen, N., Chen, Z. J., Whelan, S. P., Fransen, M., Nibert, M. L., Superti-Furga, G., and Kagan, J. C. (2010) Cell 141, 668-681,

Speaker: Wan-Ying, Lin (林宛瑩)                                                 Time: 14:00~15:00, Nov. 3, 2010

Commentator: Chun-Keung Yu, Ph.D. (余俊強老師)         Place: Room 601

Abstract:

        To protect cell from viral evasion, mitochondrial adaptor protein MAVS revives the signal from cytosolic RIG-I-like receptors (RLRs), which are responsible for detecting viral RNA (vRNA) species, and then trigger antiviral immune responses. MAVS locates in the mitochondrial outer membrane and its location is necessary for signaling (1). This points the concept that RLRs use the cellular organelle to transmit stimuli from cytosol for initiating the innate immune response. Mitochondria have been reported to have intimate functional relationship with peroxisomes in lipid metabolism and their biogenesis (2). While mitochondria are well-established sites of antiviral responses, the role of peroxisomes in innate immune signaling is still known. MAVS has a similar structure with Fis1 and Mff, which locate in peroxisomal and mitochondrial membranes to regulate the morphology of both organelles. In this study, the authors linked MAVS to peroxisomes in antiviral signaling. First, this work indicated that MAVS resided in both peroxisomes and mitochondria. To determine the function of peroxisomal MAVS, the authors generated different cell lines expressing MAVS with C-terminal localization motif deleted or replaced with other motif for targeting it to known compartments. Peroxisomal and mitochondrial MAVS both induced the expression of viperin, a well-characterized ISG (interferon-stimulated gene), in Reovirus-infected cells. The peroxisomal MAVS led to early and transient ISG induction, while the mitochondrial MAVS induced interferon-dependent ISG through delayed kinetics. The interferon regulatory IRF1 was required for the expression of ISG by peroxisomal MAVS. Together, peroxisomal MAVS induce a rapid and short term protection independent of type I IFNs during viral infection. This work also establishes that peroxisomes are important platforms for antiviral innate immunity.

References:

1. Seth, R. B., Sun, L., Ea, C. K., and Chen, Z. J. (2005) Cell 122, 669-682

2. Hettema, E. H., and Motley, A. M. (2009) J Cell Sci 122, 2331-2336