Figure 4.

Plausible role of prohibitin in mitochondrial Ca²⁺ overload. During hyperglycemic condition, there is a remarkable increase in cytosolic Ca²⁺ (Ca²⁺)_c. Physiologically, the elevation of (Ca²⁺)_c is required for maintaining the normal metabolic pathways; however, persistent elevation leads to the movement of the (Ca²⁺)_c to the mitochondria and the subsequent rise in mitochondrial Ca²⁺ (Ca²⁺)_m concentration. Prohibitin may attempt to buffer this excess of (Ca²⁺)_m to further prevent the mitochondrial-mediated apoptosis by preventing the release of cytochrome c (Cyt c). The consequence of this event may lead to decreased cellular function, β-cell loss, and diabetes. Overexpression of prohibitin may help in sequestering excess of the Ca²⁺ and prevent apoptosis. Mitochondrial calcium uniporter (MCU) and voltage-dependent anion channel (VDAC) are the channels on the inner and outer surface of mitochondria that sequesters the (Ca²⁺)_m cooperatively.