Peroxisomes are signaling platforms for antiviral innate immunity
By Evelyn Dixit, S. Boulant, Yijing Zhang, A. S. Lee, Charlotte Odendall, Bennett O. V. Shum, Nir Hacohen, Zhijian J. Chen, S. Whelan, M. Fransen and 3 more. Cell, 2010
824 citations recorded by the source corpus.
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.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/95347ad1c95e0898982ca8969ec1ba81c3cc9ab8
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
In Molecular Biology
Citations in the corpus
- Innate Immune Pattern Recognition: A Cell Biological Perspective (2015, neutral): “Variants of MAVS lacking this domain are incapable of inducing an IFN signal, although they contain the necessary regions for interaction with downstream signaling proteins (24, 25).”
- Mitochondria in the regulation of innate and adaptive immunity (2015, neutral): “It is important to note that MAVS is also localized to the membranes of peroxisomes, which is necessary for the rapid early but transient expression of antiviral genes called interferon-stimulated genes (ISGs) (Dixit et al., 2010).”
- Pathogen Recognition by the Innate Immune System (2011, background): “Macrophages and DCs stimulated with TLR3 and TLR4 PAMPs trigger TRIFdependent signaling, which leads to the production of proinflammatory cytokines and type I interferons via activation of NF-κB, MAP kinases and IRF3 (Fig.”
- CD14 controls the LPS-induced endocytosis of Toll-like Receptor 4 (2011, neutral): “IFN activity was measured as described (Dixit et al., 2010).”
- Immune signaling by RIG-I-like receptors (2011, methodology): “Reports have placed IPS-1 on the outer membranes of the mitochondria, the membranes of peroxisomes, and mitochondria-associated membranes (Scott, 2010; Dixit et al., 2010; unpublished observations).”
- MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response (2011, background): “Though the vast majority of MAVS is located on the mitochondrial membrane, a very small fraction of MAVS is located on the peroxisomal membrane (Dixit et al., 2010).”
- Cytosolic Sensing of Viruses (2013, background): “Verterbrate cells have evolved a vast arsenal of viral restriction factors that directly inhibit all steps of viral replication (Duggal and Emerman, 2012; Yan and Chen, 2012; Garcı́a-Sastre, 2011) (Figure 1).”
- Interferon-stimulated genes and their antiviral effector functions (2011, neutral): “Mechanistically, this IFN-independent IRF1 antiviral phenotype has been linked to signaling from the RIG-I-like receptor adapter protein IPS1 localized specifically on peroxisomes, but not mitochondria[36].”