Endoplasmic Reticulum-mitochondria connections, calcium cross-talk and cell fate: a closer inspection.

In eukaryotic cells, calcium (Ca2+) stores form a complex web where the capability to take up and release the cation is spread among different but highly interconnected structures that are physically based on the most abundant intracellular membranes: i.e., those forming the endoplasmic reticulum (ER) and the mitochondrial networks. Main hubs of these infra-structures are the Mitochondria-Associated Membranes (MAMs), ER and mitochondria juxtaposed membrane domains whose precise composition and functionality are now emerging. Understanding how these intracellular networks control Ca2+ dynamics under physiological and pathological conditions is fundamental to life sciences. The relevance of this issue is documented by the extraordinarily large number of qualified contributions that can offer both extensive reviews and in-depth examinations of specific aspects. Here we update the ER-mitochondria connection, with a special glance at the Ca2+ cross-talk, from different points of view: the molecules that are involved, either as essential building blocks or as modulators; the messages that travel between the two networks; the most novel technical approaches that allow to answer old questions and open new perspectives.