Endoplasmic reticulum, Bcl-2 and Ca2+ handling in apoptosis

In the complex signalling interplay that allows extracellular signals to be decoded into activation of apoptotic cell death, Ca²⁺ plays a significant role. This is supported not only by evidence linking alterations in Ca²⁺ homeostasis to the triggering of apoptotic (and in some cases necrotic) cell death, but also by recent data indicating that a key anti-apoptotic protein, Bcl-2, has a direct effect on ER Ca²⁺ handling. We will briefly summarise the first aspect, and describe in more detail these new data, demonstrating that (i) Bcl-2 reduces the state of filling of the ER Ca²⁺ store and (ii) this Ca²⁺ signalling alteration renders the cells less sensitive to apoptotic stimuli. Overall, these results suggest that calcium homeostasis may represent a pharmacological target in the fundamental pathological process of apoptosis.