ER-to-lysosome Ca²⁺ refilling followed by K⁺ efflux-coupled store-operated Ca²⁺ entry in inflammasome activation and metabolic inflammation.

ABSTRACT: We studied lysosomal Ca²⁺ in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca²⁺ ([Ca²⁺]_Lys) and increased [Ca²⁺]_i through mitochondrial ROS, which was suppressed in Trpm2-KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated by Trpm2 KO. ER→lysosome Ca²⁺ refilling occurred after lysosomal Ca²⁺ release whose blockade attenuated LPS + PA-induced inflammasome. Subsequently, store-operated Ca²⁺entry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K⁺ efflux whose inhibition reduced ER Ca²⁺ content ([Ca²⁺

SUBMITTER: Kang H 

PROVIDER: S-EPMC11219040 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature