TitleStore-Operated Ca Entry Controls Induction of Lipolysis and the Transcriptional Reprogramming to Lipid Metabolism.
Publication TypeJournal Article
Year of Publication2017
AuthorsMaus M, Cuk M, Patel B, Lian J, Ouimet M, Kaufmann U, Yang J, Horvath R, Hornig-Do H-T, Chrzanowska-Lightowlers ZM, Moore KJ, Cuervo AMaria, Feske S
JournalCell Metab
Date Published2017 Mar 07
KeywordsAdenylyl Cyclases, Animals, Calcium, Fatty Acids, HEK293 Cells, Humans, Lipase, Lipid Droplets, Lipolysis, Mice, Mitochondria, Muscle, Skeletal, Oxidation-Reduction, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, PPAR alpha, Signal Transduction, Transcription, Genetic, Up-Regulation

Ca signals were reported to control lipid homeostasis, but the Ca channels and pathways involved are largely unknown. Store-operated Ca entry (SOCE) is a ubiquitous Ca influx pathway regulated by stromal interaction molecule 1 (STIM1), STIM2, and the Ca channel ORAI1. We show that SOCE-deficient mice accumulate pathological amounts of lipid droplets in the liver, heart, and skeletal muscle. Cells from patients with loss-of-function mutations in STIM1 or ORAI1 show a similar phenotype, suggesting a cell-intrinsic role for SOCE in the regulation of lipid metabolism. SOCE is crucial to induce mobilization of fatty acids from lipid droplets, lipolysis, and mitochondrial fatty acid oxidation. SOCE regulates cyclic AMP production and the expression of neutral lipases as well as the transcriptional regulators of lipid metabolism, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), and peroxisome proliferator-activated receptor α (PPARα). SOCE-deficient cells upregulate lipophagy, which protects them from lipotoxicity. Our data provide evidence for an important role of SOCE in lipid metabolism.

Alternate JournalCell Metab.
PubMed ID28132808
PubMed Central IDPMC5342942
Grant ListR01 HL119047 / HL / NHLBI NIH HHS / United States
P30 CA016087 / CA / NCI NIH HHS / United States
G1000848 / / Medical Research Council / United Kingdom
P30 DK041296 / DK / NIDDK NIH HHS / United States
R01 AI097302 / AI / NIAID NIH HHS / United States
309548 / / European Research Council / International
P30 AG038072 / AG / NIA NIH HHS / United States
/ / Wellcome Trust / United Kingdom
P01 AG031782 / AG / NIA NIH HHS / United States