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

ABSTRACT: Aberrant activation of NLRP3 inflammasome has an important function in the pathogenesis of various inflammatory diseases. Although many components and mediators of inflammasome activation have been identified, how NLRP3 inflammasome is regulated to prevent excessive inflammation is unclear. Here we show NLRP3 inflammasome stimulators trigger Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) translocation to the mitochondria, to interact with and dephosphorylate adenine nucleotide translocase 1 (ANT1), a central molecule controlling mitochondrial permeability transition. This mechanism prevents collapse of mitochondrial membrane potential and the subsequent release of mitochondrial DNA and reactive oxygen species, thus preventing hyperactivation of NLRP3 inflammasome. A

SUBMITTER: Guo W 

PROVIDER: S-EPMC5735095 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature