Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death

The endoplasmic reticulum (ER) and mitochondria cannot be considered as static structures, as they intimately communicate, forming very dynamic platforms termed mitochondria-associated membranes (MAMs). In particular, the ER transmits proper Ca²⁺ signals to mitochondria, which decode them into specific inputs to regulate essential functions, including metabolism, energy production and apoptosis. Here, we will describe the different molecular players involved in the transfer of Ca²⁺ ions from the ER lumen to the mitochondrial matrix and how modifications in both ER-mitochondria contact sites and Ca²⁺ signaling can alter the cell death execution program.