Regulation of autophagy by Ca2+

Autophagy is an evolutionarily conserved lysosomal catabolic process used as an internal engine in response to nutrient starvation or metabolic stress. A number of protein complexes and an intricate network of stress signaling cascades impinge on the regulation of autophagy; the mammalian target of rapamycin serves as a canonical player. Ca2+, as a major intracellular second messenger, regulates multiple physiological and pathological functions. Although significant information is already well-established about the role of Ca2+ in apoptosis, its role in autophagy has been recently determined and is poorly understood. Intracellular Ca2+ positively and negatively affects autophagy. In this review, evidence for both views and the interplay of Ca2+ between autophagy and apoptosis induction are discussed. The available data revealed the bidirectional role of Ca2+ in the regulation of autophagy. Moreover, the data also indicated that this role probably depends on the context of time, space, Ca2+ source, and cell state, thus either preventing or enhancing autophagy.