Open AccessLoss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
Author(s) -
Wen-An Wang,
Wenxin Liu,
Serpen Durnaoglu,
Sun-Kyung Lee,
Jihong Lian,
Richard Lehner,
Joohong Ahnn,
Luis B. Agellon,
Marek Michalak
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-05734-x
Subject(s) - homeostasis , calreticulin , sterol , microbiology and biotechnology , cholesterol , basal (medicine) , calcium , iron homeostasis , lipid metabolism , biology , chemistry , biochemistry , endoplasmic reticulum , endocrinology , metabolism , organic chemistry , insulin
A direct link between Ca 2+ and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca 2+ causes the re-distribution of a portion of the intracellular unesterified cholesterol to a pool that is not available to the SCAP-SREBP complex. The SREBP processing pathway in ER Ca 2+ depleted cells remained fully functional and responsive to changes in cellular cholesterol status but differed unexpectedly in basal activity. These findings establish the role of Ca 2+ in determining the reference set-point for controlling cellular lipid homeostasis. We propose that ER Ca 2+ status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway.