A Putative Prohibitin-Calcium Nexus In Beta-Cell Mitochondria And Diabetes

The role of mitochondria in apoptosis is well known; however, the mechanisms linking mitochondria to the proapoptotic effects of proinflammatory cytokines, hyperglycemia, and glucolipotoxicity are not completely understood. Complex Ca(2+)signaling has emerged as a critical contributor to these proapoptotic effects and has gained significant attention in regulating the signaling processes of mitochondria. In pancreatic beta-cells, Ca(2+)plays an active role in beta-cell function and survival. Prohibitin (PHB), a mitochondrial chaperone, is actively involved in maintaining the architecture of mitochondria. However, its possible interaction with Ca2+-activated signaling pathways has not been explored. The present review aims to examine potential crosstalk between Ca(2+)signaling and PHB function in pancreatic beta-cells. Moreover, this review will focus on the effects of cytokines and glucolipotoxicity on Ca(2+)signaling and its possible interaction with PHB. Improved understanding of this important mitochondrial protein may aid in the design of more targeted drugs to identify specific pathways involved with stress-induced dysfunction in the beta-cell.