title: Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane.
abstract: A rise of the intracellular Ca(2+) concentration has multiple signaling functions. Sustained Ca(2+) influx across plasma membrane through calcium release-activated calcium (CRAC) channels is required for T-cell development in the thymus, gene transcription, and proliferation and differentiation of naïve T-cells into armed effectors cells. Intracellular Ca(2+) signals are shaped by mitochondria, which function as a highly dynamic Ca(2+) buffer. However, the precise role of mitochondria for Ca(2+)-dependent T-cell activation is unknown. Here we have shown that mitochondria are translocated to the plasma membrane as a consequence of Ca(2+) influx and that this directed movement is essential to sustain Ca(2+) influx through CRAC channels. The decreased distance between mitochondria and the plasma membrane enabled mitochondria to take up large amounts of inflowing Ca(2+) at the plasma membrane, thereby preventing Ca(2+)-dependent inactivation of CRAC channels and sustaining Ca(2+) signals. Inhibition of kinesin-dependent mitochondrial movement along microtubules abolished mitochondrial translocation and reduced sustained Ca(2+) signals. Our results show how a directed movement of mitochondria is used to control important cellular functions such as Ca(2+)-dependent T-cell activation.
authors.affiliation: Department of Physiology, Institute for Molecular Cell Biology, Saarland University, 66421 Homburg, Germany. ptaqgo@uniklinikum-saarland.de
authors.forename: Ariel
authors.initials: A
authors.lastname: Quintana
authors.forename: Eva C
authors.initials: EC
authors.lastname: Schwarz
authors.forename: Christian
authors.initials: C
authors.lastname: Schwindling
authors.forename: Peter
authors.initials: P
authors.lastname: Lipp
authors.forename: Lars
authors.initials: L
authors.lastname: Kaestner
authors.forename: Markus
authors.initials: M
authors.lastname: Hoth
mesh_terms: D001693:Biological Transport, Active / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D016547:Kinesins / Q000502:physiology; D008870:Microtubules; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology
chemical_list: D015220:Calcium Channels; D016547:Kinesins; D002118:Calcium