Endoplasmic reticulum calcium dictates the distribution of intracellular unesterified cholesterol

Endoplasmic reticulum (ER) luminal Ca²⁺ influences many functions of this organelle, notably the synthesis and quality control of proteins and lipids. Cholesterol is an essential component of biological membranes and a precursor for many biologically important signaling molecules. The sterol regulatory element-binding proteins (SREBPs) are key regulators of lipid metabolism. These transcription factors are synthesized as ER membrane-bound precursor proteins that are proteolytically processed in response to cellular cholesterol status. Recently, ER Ca²⁺ status was shown to be an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway. This article discusses the emerging relationship between cellular Ca²⁺ and cholesterol metabolism.