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Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis.

ABSTRACT: A direct link between Ca²⁺ and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ in determining the reference set-point for controlling cellular lipid homeostasis. We propose that ER Ca²⁺ status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway.

SUBMITTER: Wang WA

PROVIDER: S-EPMC5517566 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis.

Wang Wen-An WA Liu Wen-Xin WX Durnaoglu Serpen S Lee Sun-Kyung SK Lian Jihong J Lehner Richard R Ahnn Joohong J Agellon Luis B LB Michalak Marek M

Scientific reports 20170719 1

A direct link between Ca2+ and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca2+ 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 Ca2+ depleted cells remained fully functional and responsive to changes in cellular cholesterol status but differed unexpectedly in basal activity ...[more]

PMID: 28725049

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