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. 2017 Jul 19;7:5941. doi: 10.1038/s41598-017-05734-x

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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A schematic representation depicting the role of Ca²⁺ on intracellular cholesterol distribution. The model shows cross-talk between endoplasmic reticulum (ER) Ca²⁺ and intracellular cholesterol distribution. The majority of unesterified cholesterol (Chol) in the cell is localized in the plasma membrane (PM) and the remainder is found in ER membranes where it regulates the processing of SREBP. Under cholesterol replete conditions (left) SREBP processing is limited. Reducing ER luminal Ca²⁺ (right) enriches a distinct intracellular pool of cholesterol. The decrease in the ER membrane cholesterol enhances SREBP processing and increases the abundance of SREBP in the nucleus.