Module 5: Figure ER/mitochondrial shuttle
The endoplasmic reticulum (ER)/mitochondrial Ca2+ shuttle.
The endoplasmic reticulum (ER) and the mitochondria are functionally linked through their participation in Ca2+ signalling. During Ca2+ signalling, a small bolus of Ca2+ is periodically released to the cytoplasm by the inositol 1,4,5-trisphosphate receptors (InsP3Rs). While most of the Ca2+ is returned to the ER by the sarco/endo-plasmic reticulum Ca2+-ATPase (SERCA) pump, a proportion enters the mitochondria through the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane (OMM), and then through the uniporter in the inner mitochondrial membrane (IMM). Mitochondrial calcium uptake 1 (MICU1) may regulate the uniporter. The Ca2+ in the mitochondrial matrix is then returned to the ER through a series of exchangers, channels and pumps. Firstly, Ca2+ leaves the matrix through a Na+/Ca2+ exchanger and then enters the cytoplasm through the VDAC. Once in the cytoplasm, it can be taken back into the ER by the SERCA pumps.