title: Modulation of Calcium Entry by Mitochondria.
abstract: The role of mitochondria in intracellular Ca(2+) signaling relies mainly in its capacity to take up Ca(2+) from the cytosol and thus modulate the cytosolic [Ca(2+)]. Because of the low Ca(2+)-affinity of the mitochondrial Ca(2+)-uptake system, this organelle appears specially adapted to take up Ca(2+) from local high-Ca(2+) microdomains and not from the bulk cytosol. Mitochondria would then act as local Ca(2+) buffers in cellular regions where high-Ca(2+) microdomains form, that is, mainly close to the cytosolic mouth of Ca(2+) channels, both in the plasma membrane and in the endoplasmic reticulum (ER). One of the first targets proposed already in the 1990s to be regulated in this way by mitochondria were the store-operated Ca(2+) channels (SOCE). Mitochondria, by taking up Ca(2+) from the region around the cytosolic mouth of the SOCE channels, would prevent its slow Ca(2+)-dependent inactivation, thus keeping them active for longer. Since then, evidence for this mechanism has accumulated mainly in immunitary cells, where mitochondria actually move towards the immune synapse during T cell activation. However, in many other cell types the available data indicate that the close apposition between plasma and ER membranes occurring during SOCE activation precludes mitochondria from getting close to the Ca(2+)-entry sites. Alternative pathways for mitochondrial modulation of SOCE, both Ca(2+)-dependent and Ca(2+)-independent, have also been proposed, but further work will be required to elucidate the actual mechanisms at work. Hopefully, the recent knowledge of the molecular nature of the mitochondrial Ca(2+) uniporter will allow soon more precise studies on this matter.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Ramon y Cajal 7, 47005, Valladolid, Spain.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Fonteriz
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Ramon y Cajal 7, 47005, Valladolid, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Matesanz-Isabel
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Ramon y Cajal 7, 47005, Valladolid, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Arias-Del-Val
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Ramon y Cajal 7, 47005, Valladolid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Alvarez-Illera
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Ramon y Cajal 7, 47005, Valladolid, Spain.
authors.forename: Mayte
authors.initials: M
authors.lastname: Montero
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Ramon y Cajal 7, 47005, Valladolid, Spain. jalvarez@ibgm.uva.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008928:Mitochondria / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D002118:Calcium
keywords: CRAC channels; Ca2+ microdomain; Ca2+ uniporter; Endoplasmic reticulum; MCU; Mitochondria; Orai; SOCE; STIM; Store-operated Ca2+ entry