Fig. 8: Schematic diagram of Ca²⁺ homeostasis regulation by Bcl-2.

Wild-type Bcl-2 (WT) maintains high Ca²⁺ levels in the ER but low Ca²⁺ levels in cytosol and mitochondria. The three-amino acid mutation (¹⁴⁴WGR¹⁴⁶ to ¹⁴⁴AAA¹⁴⁶) in the Bcl-2 α5-helix (mutant Bcl-2, mt) depletes Ca²⁺ in the ER store but causes Ca²⁺overload in both cytosol and mitochondria. WT and mt cause different expression of SOCE-related molecules. During thapsigargin stimulation, mt-overexpressing cells presented a significant Ca²⁺ influx through SOCE and subsequent activation of ER-stress-mediated caspase activation and apoptosis. In contrast, WT-overexpressing cells decreases thapsigargin-induced SOCE and intracellular Ca²⁺ elevation which protects cells against apoptosis