Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane

A rise of the intracellular Ca2+ concentration has multiple signaling functions. Sustained Ca2+ 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 naive T-cells into armed effectors cells. Intracellular Ca2+ signals are shaped by mitochondria, which function as a highly dynamic Ca2+ buffer. However, the precise role of mitochondria for Ca2+-dependent T-cell activation is unknown. Here we have shown that mitochondria are translocated to the plasma membrane as a consequence of Ca2+ influx and that this directed movement is essential to sustain Ca2+ influx through CRAC channels. The decreased distance between mitochondria and the plasma membrane enabled mitochondria to take up large amounts of inflowing Ca2+ at the plasma membrane, thereby preventing Ca2+-dependent inactivation of CRAC channels and sustaining Ca2+ signals. Inhibition of kinesin-dependent mitochondrial movement along microtubules abolished mitochondrial translocation and reduced sustained Ca2+ signals. Our results show how a directed movement of mitochondria is used to control important cellular functions such as Ca2+-dependent T-cell activation.