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Store-Operated Ca2+ Entry Controls Induction of Lipolysis and the Transcriptional Reprogramming to Lipid Metabolism

Lookup NU author(s): Professor Rita Horvath, Dr Hue Hornig - Do, Professor Zofia Chrzanowska-Lightowlers

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2017 Elsevier Inc. Ca2+ signals were reported to control lipid homeostasis, but the Ca2+ channels and pathways involved are largely unknown. Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ influx pathway regulated by stromal interaction molecule 1 (STIM1), STIM2, and the Ca2+ 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.


Publication metadata

Author(s): Maus 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 AM, Feske S

Publication type: Article

Publication status: Published

Journal: Cell Metabolism

Year: 2017

Volume: 25

Issue: 3

Pages: 698-712

Print publication date: 07/03/2017

Online publication date: 26/01/2017

Acceptance date: 28/12/2016

Date deposited: 18/07/2017

ISSN (print): 1550-4131

ISSN (electronic): 1932-7420

Publisher: Cell Press

URL: https://doi.org/10.1016/j.cmet.2016.12.021

DOI: 10.1016/j.cmet.2016.12.021


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