Acidic intracellular Ca2+ stores and caveolae in Ca2+ signaling and diabetes

Acidic Ca2+ stores, particularly lysosomes, are newly discovered players in the well-orchestrated arena of Ca2+ signaling and we are at the verge of understanding how lysosomes accumulate Ca2+ and how they release it in response to different chemical, such as NAADP, and physical signals. Additionally, it is now clear that lysosomes play a key role in autophagy, a process that allows cells to recycle components or to eliminate damaged structures to ensure cellular well-being. Moreover, lysosomes are being unraveled as hubs that coordinate both anabolism via insulin signaling and catabolism via AMPK. These acidic vesicles have close contact with the ER and there is a bidirectional movement of information between these two organelles that exquisitely regulates cell survival. Lysosomes also connect with plasma membrane where caveolae are located as specialized regions involved in Ca2+ and insulin signaling. Alterations of all these signaling pathways are at the core of insulin resistance and diabetes.