Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca(2+) uptake. Here we clarify the molecular mechanism that determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake. Our data demonstrate that mitochondrial Ca(2+) uptake is controlled by protein arginine methyl transferase 1 (PRMT1) that asymmetrically methylates MICU1, resulting in decreased Ca(2+) sensitivity. UCP2/3 normalize Ca(2+) sensitivity of methylated MICU1 and, thus, re-establish mitochondrial Ca(2+) uptake activity. These data provide novel insights in the complex regulation of the mitochondrial Ca(2+) uniporter by PRMT1 and UCP2/3.

中文翻译：

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PRMT1介导的MICU1甲基化确定永生化细胞中线粒体Ca（2+）摄取的UCP2 / 3依赖性。

最近的研究表明，控制能量流，细胞信号传导和死亡的线粒体Ca（2+）通道是大分子复合物，主要由形成孔的线粒体Ca（2+）单向转运蛋白（MCU）蛋白，必需的MCU调节剂（ EMRE）和线粒体Ca（2+）摄取1（MICU1）。MICU1是一个调节亚基，可保护线粒体免受Ca（2+）超负荷的影响。在确定这些核心元素之前，新型的解偶联蛋白2和3（UCP2 / 3）已被证明是线粒体Ca（2+）吸收的基础。在这里，我们阐明了决定线粒体Ca（2+）吸收的UCP2 / 3依赖性的分子机制。我们的数据表明，线粒体Ca（2+）的摄取受蛋白质精氨酸甲基转移酶1（PRMT1）的控制，该蛋白质不对称地甲基化MICU1，导致Ca（2+）敏感性降低。UCP2 / 3标准化甲基化的MICU1的Ca（2+）敏感性，并因此重新建立线粒体Ca（2+）的吸收活性。这些数据提供了由PRMT1和UCP2 / 3对线粒体Ca（2+）单向转运体的复杂调控的新颖见解。