title: Endoplasmic reticulum-mitochondria coupling: local Ca²⁺ signalling with functional consequences.
abstract: Plasma membrane store-operated Ca²⁺ release-activated Ca²⁺ (CRAC) channels are a widespread and conserved Ca²⁺ influx pathway, driving activation of a range of spatially and temporally distinct cellular responses. Although CRAC channels are activated by the loss of Ca²⁺ from the endoplasmic reticulum, their gating is regulated by mitochondria. Through their ability to buffer cytoplasmic Ca²⁺, mitochondria take up Ca²⁺ released from the endoplasmic reticulum by InsP₃ receptors, leading to more extensive store depletion and stronger activation of CRAC channels. Mitochondria also buffer Ca²⁺ that enters through CRAC channels, reducing Ca²⁺-dependent slow inactivation of the channels. In addition, depolarised mitochondria impair movement of the CRAC channel activating protein STIM1 across the endoplasmic reticulum membrane. Because they regulate CRAC channel activity, particularly Ca²⁺-dependent slow inactivation, mitochondria influence CRAC channel-driven enzyme activation, secretion and gene expression. Mitochondrial regulation of CRAC channels therefore provides an important control element to the regulation of intracellular Ca²⁺ signalling.
authors.affiliation: Department of Physiology, Anatomy and Genetics Sherrington Building, South Parks Road, Oxford, OX1 3PT, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bakowski
authors.forename: Charmaine
authors.initials: C
authors.lastname: Nelson
authors.forename: Anant B
authors.initials: AB
authors.lastname: Parekh
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D015640:Ion Channel Gating; D008407:Mast Cells / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse; D002118:Calcium