The roles of mitochondria in global and local intracellular calcium signalling.

Activation of Ca channels in Ca stores in organelles and the plasma membrane generates cytoplasmic calcium ([Ca]) signals that control almost every aspect of cell function, including metabolism, vesicle fusion and contraction. Mitochondria have a high capacity for Ca uptake and chelation, alongside efficient Ca release mechanisms. Still, mitochondria do not store Ca in a prolonged manner under physiological conditions and lack the capacity to generate global [Ca] signals. However, mitochondria take up Ca at high local [Ca] signals that originate from neighbouring organelles, and also during sustained global elevations of [Ca]. Accumulated Ca in the mitochondria stimulates oxidative metabolism and upon return to the cytoplasm, can produce spatially confined rises in [Ca] to exert control over processes that are sensitive to Ca. Thus, the mitochondrial handling of [Ca] is of physiological relevance. Furthermore, dysregulation of mitochondrial Ca handling can contribute to debilitating diseases. We discuss the mechanisms and relevance of mitochondria in local and global calcium signals.