Fig. 5.

Ca²⁺ transfer from ER to mitochondria at the MAM sites. Ca²⁺ released from ER through IP₃Rs flows into mitochondria matrix through VDAC in the outer mitochondrial membranes and MCU in the inner mitochondrial membranes. Optimal levels of Ca²⁺ transfer to mitochondria is necessary for mitochondrial metabolism and energy production (left). Excessive Ca²⁺ flux into mitochondria results release of pro-apoptotic proteins into cytosol, and results in apoptosis (middle). Suppression of basal mitochondrial Ca²⁺ uptake induces reduction in ATP production and autophagy in normal cells. Autophagy is not enough for survival of cancer cells (right) [155]