Cytoplasmic and Mitochondrial Calcium Signaling: A Two-Way Relationship

Intracellular Ca2+ signals are well organized in all cell types, and trigger a variety of vital physiological processes. The temporal and spatial characteristics of cytosolic Ca2+ increases are mainly governed by the fluxes of this ion across the membrane of the endoplasmic/sarcoplasmic reticulum and the plasma membrane. However, various Ca2+ transporters also allow for Ca2+ exchanges between the cytoplasm and mitochondria. Increases in mitochondrial Ca2+ stimulate the production of ATP, which allows the cells to cope with the increased energy demand created by the stimulus. Less widely appreciated is the fact that Ca2+ handling by mitochondria also shapes cytosolic Ca2+ signals. Indeed, the frequency, amplitude, and duration of cytosolic Ca2+ increases can be altered by modifying the rates of Ca2+ transport into, or from, mitochondria. In this review, we focus on the interplay between mitochondria and Ca2+ signaling, highlighting not only the consequences of cytosolic Ca2+ changes on mitochondrial Ca2+, but also how cytosolic Ca2+ dynamics is controlled by modifications of the Ca2+-handling properties and the metabolism of mitochondria.