Store-operated Ca 2 + entry ( SOCE ) regulates lipid metabolism

A role for Ca signaling in the regulation of lipid metabolism has been suggested, but the Ca channels involved in this process remain elusive. Store-operated Ca entry (SOCE) is a ubiquitous Ca influx pathway that is regulated by the endoplasmic reticulum (ER) Ca sensors stromal interaction molecule (STIM) 1 and 2, and the plasma membrane Ca channel ORAI1. SOCE-deficient mice with abolished SOCE accumulate pathological amounts of lipid droplets in the liver, heart and skeletal muscle. Cells from patients with loss-of-function mutations in STIM1 and ORAI1 show lipid droplet accumulation, suggesting that the role of SOCE in lipid metabolism is conserved in humans. Functionally, SOCE contributes to regulating levels and usage of intracellular lipids by modulating lipolysis, lipophagy and mitochondrial function. Mechanistically, SOCE controls expression of PGC-1 and PPAR, master regulators of lipid metabolism. Our data demonstrate that SOCE is a crucial regulator of lipid metabolism.