title: Peroxisomes are signaling platforms for antiviral innate immunity.
abstract: Peroxisomes have long been established to play a central role in regulating various metabolic activities in mammalian cells. These organelles act in concert with mitochondria to control the metabolism of lipids and reactive oxygen species. However, while mitochondria have emerged as an important site of antiviral signal transduction, a role for peroxisomes in immune defense is unknown. Here, we report that the RIG-I-like receptor (RLR) adaptor protein MAVS is located on peroxisomes and mitochondria. We find that peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. The interferon regulatory factor IRF1 plays a crucial role in regulating MAVS-dependent signaling from peroxisomes. These results establish that peroxisomes are an important site of antiviral signal transduction.
authors.affiliation: Division of Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Dixit
authors.forename: Steeve
authors.initials: S
authors.lastname: Boulant
authors.forename: Yijing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Amy S Y
authors.initials: AS
authors.lastname: Lee
authors.forename: Charlotte
authors.initials: C
authors.lastname: Odendall
authors.forename: Bennett
authors.initials: B
authors.lastname: Shum
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Zhijian J
authors.initials: ZJ
authors.lastname: Chen
authors.forename: Sean P
authors.initials: SP
authors.lastname: Whelan
authors.forename: Marc
authors.initials: M
authors.lastname: Fransen
authors.forename: Max L
authors.initials: ML
authors.lastname: Nibert
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Kagan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism*; D015398:Signal Transduction; D014709:Vero Cells
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007372:Interferons; C512612:MAVS protein, mouse; C505371:MAVS protein, human
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