Internal Medicine

Sutterwala paper on cover of Immunity

Sutterwala Cover 8-29-13

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.

Abstract:
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 cardiolipin.

Read the journal article online.