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

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