Peroxisomes are signaling platforms for antiviral innate immunity

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 sit...

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Published in:Cell Vol. 141; no. 4; p. 668
Main Authors: Dixit, Evelyn, Boulant, Steeve, Zhang, Yijing, Lee, Amy S Y, Odendall, Charlotte, Shum, Bennett, Hacohen, Nir, Chen, Zhijian J, Whelan, Sean P, Fransen, Marc, Nibert, Max L, Superti-Furga, Giulio, Kagan, Jonathan C
Format: Journal Article
Language:English
Published: United States 14.05.2010
Subjects:
Adaptor Proteins, Signal Transducing - immunology
Adaptor Proteins, Signal Transducing - metabolism
Animals
Cell Line
Cercopithecus aethiops
Fibroblasts - metabolism
Hepatocytes - metabolism
Humans
Immunity, Innate
Interferons - metabolism
Mice
Mitochondria - metabolism
Peroxisomes - metabolism
Signal Transduction
Vero Cells
ISSN:1097-4172, 1097-4172
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Summary: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.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2010.04.018