@article{585b60e9b44348d0a7220011b80412f0,
title = "Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation",
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 themitochondrial lipid cardiolipin. Cardiolipin bound toNlrp3 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.",
author = "Iyer, {Shankar S.} and Qiong He and Janczy, {John R.} and Elliott, {Eric I.} and Zhenyu Zhong and Olivier, {Alicia K.} and Sadler, {Jeffrey J.} and Vickie Knepper-Adrian and Renzhi Han and Liang Qiao and Eisenbarth, {Stephanie C.} and Nauseef, {William M.} and Cassel, {Suzanne L.} and Sutterwala, {Fayyaz S.}",
note = "Funding Information: We thank R. Flavell, J. Bertin, and Millennium Pharmaceuticals for providing knockout mice, F. Martinon for providing Flag-tagged Nlrp3 constructs, T. Gioannini for providing His-tagged TLR4, and P. Rothman and R. Mallampalli for helpful discussion. National Institutes of Health grants R01 AI087630 (F.S.S.), K08 AI067736 (S.L.C.), R01 AR064241 (R.H.), R01 HL116546 (R.H.), and T32 AI007485 (J.R.J.), American Heart Association Scientist Development Grant 10SDG4140138 (R.H.), Muscular Dystrophy Association grant MDA171667 (R.H.), Asthma and Allergy Foundation of America fellowship (S.L.C.), and an Edward Mallinckrodt, Jr. Foundation scholarship (F.S.S.) supported this work. The Inflammation Program (W.M.N., S.L.C., and F.S.S.) is supported by resources and use of facilities at the Veterans Affairs Medical Center, Iowa City, IA. ",
year = "2013",
month = aug,
day = "22",
doi = "10.1016/j.immuni.2013.08.001",
language = "English (US)",
volume = "39",
pages = "311--323",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",
}
