Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis

The NLRP3 inflammasome is central to a variety of inflammatory diseases, but how it is regulated to prevent excessive inflammation is not clear. Here the authors show that NLRP3 activation causes SHP2 translocation to the mitochondria to interact with and dephosphorylate ANT1, thus stabilizing the m...

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Main Authors:	Wenjie Guo, Wen Liu, Zhen Chen, Yanhong Gu, Shuang Peng, Lihong Shen, Yan Shen, Xingqi Wang, Gen-Sheng Feng, Yang Sun, Qiang Xu
Format:	Article
Language:	English
Published:	Nature Publishing Group 2017-12-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-017-02351-0

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record_format	Article
spelling	doaj-5f5f911797374397b243eef9239a9a182021-05-11T07:14:47ZengNature Publishing GroupNature Communications2041-17232017-12-018111410.1038/s41467-017-02351-0Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasisWenjie Guo0Wen Liu1Zhen Chen2Yanhong Gu3Shuang Peng4Lihong Shen5Yan Shen6Xingqi Wang7Gen-Sheng Feng8Yang Sun9Qiang Xu10State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityDepartment of Diabetes Complications and Metabolism, Beckman Research Institute of City of HopeDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical UniversityState Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityDepartment of Pathology, and Division of Biological Sciences, University of California San DiegoState Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing UniversityThe NLRP3 inflammasome is central to a variety of inflammatory diseases, but how it is regulated to prevent excessive inflammation is not clear. Here the authors show that NLRP3 activation causes SHP2 translocation to the mitochondria to interact with and dephosphorylate ANT1, thus stabilizing the mitochondria and preventing release of proinflammatory mitochondrial DNA and ROS.https://doi.org/10.1038/s41467-017-02351-0
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Wenjie Guo Wen Liu Zhen Chen Yanhong Gu Shuang Peng Lihong Shen Yan Shen Xingqi Wang Gen-Sheng Feng Yang Sun Qiang Xu
spellingShingle	Wenjie Guo Wen Liu Zhen Chen Yanhong Gu Shuang Peng Lihong Shen Yan Shen Xingqi Wang Gen-Sheng Feng Yang Sun Qiang Xu Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis Nature Communications
author_facet	Wenjie Guo Wen Liu Zhen Chen Yanhong Gu Shuang Peng Lihong Shen Yan Shen Xingqi Wang Gen-Sheng Feng Yang Sun Qiang Xu
author_sort	Wenjie Guo
title	Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis
title_short	Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis
title_full	Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis
title_fullStr	Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis
title_full_unstemmed	Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis
title_sort	tyrosine phosphatase shp2 negatively regulates nlrp3 inflammasome activation via ant1-dependent mitochondrial homeostasis
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2017-12-01
description	The NLRP3 inflammasome is central to a variety of inflammatory diseases, but how it is regulated to prevent excessive inflammation is not clear. Here the authors show that NLRP3 activation causes SHP2 translocation to the mitochondria to interact with and dephosphorylate ANT1, thus stabilizing the mitochondria and preventing release of proinflammatory mitochondrial DNA and ROS.
url	https://doi.org/10.1038/s41467-017-02351-0
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Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis

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