Figure 1.

Major Ca²⁺ transporters and channels at the mitochondrion and ER. Ca²⁺ released upon the activation of IP3 receptors or ryanodine receptors at the ER is taken up into mitochondria via VDAC and Ca²⁺ uniporters at the OMM and IMM, respectively. Ca²⁺ extrusion from mitochondria is mediated via Na²⁺-dependent and Na²⁺-independent mechanisms. The Ca²⁺/Na⁺ exchanger responsible for the Na⁺-dependent mechanism has been extensively studied, whereas the characteristics of the molecule involved in Na²⁺-independent mechanism is elusive (indicated by?). The H⁺ gradient established by the Na⁺/H⁺ exchanger is thought to be important for the Na²⁺-dependent mechanism. PTP, which is often activated by pathological conditions, increases the permeability of IMM to small ions and molecules, leading to a collapse of the mitochondrial membrane potential as well as the membrane architecture. The ryanodine receptor is similar to the IP3 receptor in function except that the former is controlled under different mechanisms. Abbreviations: Ca²⁺-ATPase, ATP-dependent Ca²⁺ pump; IMM, inner mitochondrial membrane; IR3R, inositol 1,4,5-trisphosphate receptor; OMM, outer mitochondrial membrane; PTP, permeability transition pore; RYR, ryanodine receptor; VDAC, voltage-dependent anion channel.