Yes : supplementing extracellular calcium can influence both apoptosis and autophagy, but the outcome depends on cell type, calcium concentration, and context. Moderate increases in extracellular calcium can help maintain intracellular calcium homeostasis, support mitochondrial function, and activate pro-survival signaling pathways (e.g., Ca²⁺/calmodulin-dependent kinases, PI3K/Akt), thereby reducing apoptosis in some models. However, excessive extracellular calcium can trigger calcium overload, mitochondrial permeability transition, and caspase activation, promoting apoptosis instead.
Calcium can also act as a key regulator of autophagy. Elevated cytosolic Ca²⁺ from extracellular influx or internal stores can activate autophagy through pathways such as CaMKKβ–AMPK–mTOR inhibition or ER stress-mediated signals. In certain contexts, this autophagy activation is cytoprotective, aiding cell survival under stress; in others, it can contribute to autophagic cell death. Thus, extracellular calcium addition can both prevent apoptosis and activate autophagy, but the effects are highly dose- and context-dependent.
H.A Adewuyi, thank you for the clarification. I am looking to activate autophagy under autophagic inhibition conditions, by supplementing cells with extracellular calcium source, which can activate calmodulin and intern activate autophagy, cell survival and proliferation!!