Endoplasmic Reticulum Calcium Homeostasis in Kidney Disease: Pathogenesis and Therapeutic Targets

Abstract

Calcium (Ca²⁺) homeostasis is a crucial determinant of cellular function and survival. Endoplasmic reticulum (ER) acts as the largest intracellular Ca²⁺ store that maintains Ca²⁺ homeostasis through the ER Ca²⁺ uptake pump, sarco/ER Ca²⁺ ATPase, ER Ca²⁺ release channels, inositol 1,4,5-trisphosphate receptor channel, ryanodine receptor, and Ca²⁺-binding proteins inside of the ER lumen. Alterations in ER homeostasis trigger ER Ca²⁺ depletion and ER stress, which have been associated with the development of a variety of diseases. In addition, recent studies have highlighted the role of ER Ca²⁺ imbalance caused by dysfunction of sarco/ER Ca²⁺ ATPase, ryanodine receptor, and inositol 1,4,5-trisphosphate receptor channel in various kidney diseases. Despite progress in the understanding of the importance of these ER Ca²⁺ channels, pumps, and binding proteins in the pathogenesis of kidney disease, treatment is still lacking. This mini-review is focused on: i) Ca²⁺ homeostasis in the ER, ii) ER Ca²⁺ dyshomeostasis and apoptosis, and iii) altered ER Ca²⁺ homeostasis in kidney disease, including podocytopathy, diabetic nephropathy, albuminuria, autosomal dominant polycystic kidney disease, and ischemia/reperfusion-induced acute kidney injury.