Document Detail


Peroxisomes are signaling platforms for antiviral innate immunity.
MedLine Citation:
PMID:  20451243     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Evelyn Dixit; Steeve Boulant; Yijing Zhang; Amy S Y Lee; Charlotte Odendall; Bennett Shum; Nir Hacohen; Zhijian J Chen; Sean P Whelan; Marc Fransen; Max L Nibert; Giulio Superti-Furga; Jonathan C Kagan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-06
Journal Detail:
Title:  Cell     Volume:  141     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-18     Completed Date:  2010-05-20     Revised Date:  2011-03-16    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  668-81     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Division of Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE21215
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / immunology,  metabolism
Animals
Cell Line
Cercopithecus aethiops
Fibroblasts / metabolism
Hepatocytes / metabolism
Humans
Immunity, Innate*
Interferons / metabolism
Mice
Mitochondria / metabolism
Peroxisomes / metabolism*
Signal Transduction*
Vero Cells
Grant Support
ID/Acronym/Agency:
AI059371/AI/NIAID NIH HHS; R01 AI059371-06/AI/NIAID NIH HHS; R01 AI059371-07/AI/NIAID NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/IPS-1 protein, mouse; 0/VISA protein, human; 9008-11-1/Interferons
Comments/Corrections
Comment In:
Cell. 2010 May 14;141(4):570-2   [PMID:  20478250 ]
Nat Rev Immunol. 2010 Jul;10(7):465   [PMID:  20586123 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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