Adaptor MAVS Promotes NLRP3 Mitochondrial Localization and Inflammasome Activation

Abstract

NLRP3 is a key component of the macromolecular signaling complex called the inflammasome that promotes caspase 1-dependent production of IL-1β. The adaptor ASC is necessary for NLRP3-dependent inflammasome function, but it is not known whether 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 adaptor 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. Because 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.
Title: Adaptor MAVS Promotes NLRP3 Mitochondrial Localization and Inflammasome Activation
Journal: Cell
Authors: Naeha Subramanian, Kannan Natarajan, Menna R. Clatworthy, Ze Wang, and Ronald N. Germain
Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632354/