Functional role of TRP channels in modulating ER stress and Autophagy

Intracellular calcium (Ca(2+)) levels play a vital role in regulating cellular fate. The coordination and interrelation among the cellular organelles, mainly the intracellular Ca(2+) stores in endoplasmic reticulum (ER), are crucial in maintaining cytosolic Ca(2+) levels and in general cellular homeostasis. Moreover, maintaining Ca(2+) homeostasis is essential for regulating diverse and sometimes opposing processes such as cell survival and cell death in disease conditions such as, neurodegeneration, cancer and aging. Ca(2+) is able to regulate opposing functions by either regulating the cellular "self-eating" phenomenon of autophagy to promote cell survival or by regulating the programmed cell death process of apoptosis. Autophagy is also important for cell survival especially after induction of ER stress and association between ER stress and autophagy may have relevance to numerous diseases. Moreover, a multitude of evidence is emerging that the functional regulation of TRP channels, their unique localization, and their interaction with other Ca(2+)-sensing elements define these diverse regulatory pathways. It is this unique function which allows individual TRP channels to contribute differently in the regulation of cell fate and, in turn, determines the precise effect of modulating Ca(2+) signaling via the particular channel. Thus, in this review we have focused on the aspects of TRP channel localization and function (Ca(2+) signaling) that affects the ER stress and autophagic process.