Endoplasmic-reticulum calcium depletion and disease

Abstract

The endoplasmic reticulum (ER) as an intracellular Ca2+ store not only sets up cytosolic Ca2+ signals but among other functions also assembles and folds newly synthesized proteins. Alterations in ER homeostasis including severe Ca2+ depletion are an upstream event in the pathophysiology of many diseases. On the one hand insufficient release of activator Ca2+ may no longer sustain essential cell functions. On the other hand loss of luminal Ca2+ causes ER stress and activates an unfolded protein response which depending on the duration and severity of the stress can reestablish normal ER function or lead to cell death. We will review these various diseases by mainly focusing on the mechanisms that cause ER Ca2+ depletion. © 2011 Cold Spring Harbor Laboratory Press.