Figure 1.

Schematic representation of some key aspects of mitochondrial Ca²⁺ dynamics and of the interplay between Ca²⁺ and mitochondrial metabolism (A). Ca²⁺ exchanges between the cytosol and mitochondria allow the activation of mitochondrial metabolism, by boosting the Krebs cycle and the electron transport chain (ETC). (B) Membranes of the ER and the mitochondria are linked via tethering proteins (PERK, FATE, GRP75, Mfn, and others not indicated in this simplified scheme) to form mitochondria-associated membranes (MAMs). These membranes delimit areas where Ca²⁺ can reach high concentrations. (C) The electrons of the NADH produced in the cytosol by glycolysis are transferred into mitochondria by the malate-aspartate shuttle (MAS). The aspartate-glutamate carrier (AGC) of the MAS is activated by cytosolic Ca²⁺. At high mitochondrial Ca²⁺ concentration, the activation of the Krebs cycle consumes α-ketoglutarate and limits the impact of the MAS. OGC stands for oxoglutarate carrier (see text for details). (D) Ca²⁺ has to cross two membranes to enter inside a mitochondrion: the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM). The first one is passed via a voltage-dependent anion-selective channel (VDAC), a nonselective channel. More specific Ca²⁺ transporters are involved in the crossing of the IMM (see text for details).