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Mitochondria play a central role in NLRP3 inflammasome activation (349.1)
Author(s) -
Subramanian Naeha,
Natarajan Kannan,
Clatworthy Menna,
Wang Ze,
Germain Ronald
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.349.1
Subject(s) - inflammasome , mitochondrion , microbiology and biotechnology , innate immune system , cytosol , signal transducing adaptor protein , aim2 , autophagy , chemistry , secretion , signal transduction , biology , immune system , inflammation , immunology , apoptosis , biochemistry , enzyme
NLRP3 is a key component of the macromolecular signaling complex called the inflammasome that promotes caspase 1‐dependent production of IL‐1β. The adapter ASC is necessary for NLRP3‐dependent inflammasome function, but it is not known if ASC is a sufficient partner, and whether inflammasome formation occurs in the cytosol or in association with mitochondria is controversial. Here we show that the mitochondria‐associated adapter molecule, MAVS, is required for optimal NLRP3 inflammasome activity. MAVS mediates recruitment of NLRP3 to mitochondria, promoting production of IL‐1β and the pathophysiologic activity of the NLRP3 inflammasome in vivo. Our data support a more complex model of NLRP3 inflammasome activation than previously appreciated, with at least two adapters required for maximal function. Since MAVS is a mitochondria‐associated molecule previously considered to be uniquely involved in type 1 interferon production, these findings also reveal unexpected polygamous involvement of PYD/CARD domain‐containing adapters in innate immune signaling events.