Intracellular Ca 2+ signaling and Ca 2+ microdomains in the control of cell survival, apoptosis and autophagy

The endoplasmic reticulum (ER), mitochondria and lysosomes are physically and/or functionally linked, establishing close contact sites between these organelles. As a consequence, Ca2+ release events from the ER, the major intracellular Ca2+-storage organelle, have an immediate effect on the physiological function of mitochondria and lysosomes. Also, the lysosomes can act as a Ca2+ source for Ca2+ release into the cytosol, thereby influencing ER-based Ca2+ signaling. Given the important role for mitochondria and lysosomes in cell survival, cell death and cell adaptation processes, it has become increasingly clear that Ca2+ signals from or towards these organelles impact these processes. In this review, we discuss the most recent insights in the emerging role of Ca2+ signaling in cellular survival by controlling basal mitochondrial bioenergetics and by regulating apoptosis, a mitochondrial process, and autophagy, a lysosomal process, in response to cell damage and cell stress.