Mitochondrial calcium uniporter complex controls T-cell-mediated immune responses
T-cell receptor-induced Ca2+ signals are essential for proper T-cell activation and function. In this context, mitochondria play an important role and take up Ca2+ to support elevated bioenergetic demands. The protein machinery that regulates mitochondrial Ca2+ (mCa2+) uptake; the mitochondrial calcium uniporter (MCU) complex, could be thus implicated in T-cell immunity. However, the exact role of MCU in T-cells is not understood. Here, we show that upon activation of naïve T-cells, the MCU complex undergoes a compositional rearrangement that causes elevated mCa2+ uptake and increased bioenergetic output. Transcriptome and proteome analyses reveal molecular determinants involved in mitochondrial functional reprograming and identify signaling pathways controlled by MCU. MCUa knockdown diminishes mCa2+ uptake, mitochondrial respiration and ATP production as well as T-cell invasion and cytokine secretion. In vivo, downregulation of MCUa in rat CD4+ T-cells suppresses autoimmune responses in a multiple sclerosis model of inflammatory experimental autoimmune encephalomyelitis. In summary, Ca2+ uptake through MCU is essential for proper T-cell function and is involved in autoimmunity. T-cell specific MCU inhibition is a potential tool for treating autoimmune disorders. Overall design: To examine the role of MCU in T-cell mediated immune response, two RNA-seq dataset were equired. The first dataset was created to determine differences between effector and naive, human CD4 T-cells using two donors. The second  dataset was used to evaluate the function of MCU in T-cells. Therefore, a MCUa knockdown was achived using siRNA in effector CD4 T-cells. RNA-seq expression levels from two siMCU donors and two siControl donors were obtained.