| Summary: | <p>Abstract</p> <p>Calcium (Ca<sup>2+</sup>) homeostasis is fundamental for cell metabolism, proliferation, differentiation, and cell death. Elevation in intracellular Ca<sup>2+ </sup>concentration is dependent either on Ca<sup>2+ </sup>influx from the extracellular space through the plasma membrane, or on Ca<sup>2+ </sup>release from intracellular Ca<sup>2+ </sup>stores, such as the endoplasmic/sarcoplasmic reticulum (ER/SR). Mitochondria are also major components of calcium signalling, capable of modulating both the amplitude and the spatio-temporal patterns of Ca<sup>2+ </sup>signals. Recent studies revealed zones of close contact between the ER and mitochondria called MAMs (Mitochondria Associated Membranes) crucial for a correct communication between the two organelles, including the selective transmission of physiological and pathological Ca<sup>2+ </sup>signals from the ER to mitochondria. In this review, we summarize the most up-to-date findings on the modulation of intracellular Ca<sup>2+ </sup>release and Ca<sup>2+ </sup>uptake mechanisms. We also explore the tight interplay between ER- and mitochondria-mediated Ca<sup>2+ </sup>signalling, covering the structural and molecular properties of the zones of close contact between these two networks.</p>
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