Sutterwala paper on cover of Immunity
Thursday, August 29, 2013
The cover of the August issue of Immunity belongs to the paper by Fayyaz Sutterwala called "Mitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation." The cover was created by Vickie Knepper-Adrian, a research associate in Sutterwala's lab, who contributed to the paper.
Article: Mitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation
Authors: Shankar S. Iyer, Qiong He, John R. Janczy, Eric I. Elliott, Zhenyu Zhong, Alicia K. Olivier, Jeffrey J. Sadler, Vickie Knepper-Adrian, Renzhi Han, Liang Qiao, Stephanie C. Eisenbarth, William M. Nauseef, Suzanne L. Cassel, and Fayyaz S. Sutterwala
Journal: Immunity 39, 311-323, August 22, 2013; 2013 Elsevier Inc.
Nlrp3 inflammasome activation occurs in response to
numerous agonists but the specific mechanism by which this takes place remains
unclear. All previously evaluated activators of the Nlrp3 inflammasome induce
the generation of mitochondrial reactive oxygen species (ROS), suggesting a
model in which ROS is a required upstream mediator of Nlrp3 inflammasome
activation. Here we have identified the oxazolidinone antibiotic linezolid as a
Nlrp3 agonist that activates the Nlrp3 inflammasome independently of ROS. The
pathways for ROS-dependent and ROS-independent Nlrp3 activation converged upon
mitochondrial dysfunction and specifically the mitochondrial lipid cardiolipin.
Cardiolipin bound to Nlrp3 directly and interference with cardiolipin synthesis
specifically inhibited Nlrp3 inflammasome activation. Together these data
suggest that mitochondria play a critical role in the activation of the Nlrp3
inflammasome through the direct binding of Nlrp3 to
Read the journal article online.