Calcium Signaling Regulates Autophagy and Apoptosis.

Calcium (Ca) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca channels and Ca storage in various organelles is critical in maintaining cytosolic Ca levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca homeostasis is a store operated Ca entry (SOCE) mechanism that is activated by the depletion of Ca from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.