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.