Márkus Nóra M, Hasel Philip, Qiu Jing, Bell Karen F S, Heron Samuel, Kind Peter C, Dando Owen, Simpson T Ian, Hardingham Giles E
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, United Kingdom.
School of Informatics, University of Edinburgh, Edinburgh, EH8 9AB, United Kingdom.
PLoS One. 2016 Feb 1;11(2):e0148164. doi: 10.1371/journal.pone.0148164. eCollection 2016.
Uptake of Ca2+ into the mitochondrial matrix controls cellular metabolism and survival-death pathways. Several genes are implicated in controlling mitochondrial Ca2+ uptake (mitochondrial calcium regulatory genes, MCRGs), however, less is known about the factors which influence their expression level. Here we have compared MCRG mRNA expression, in neural cells of differing type (cortical neurons vs. astrocytes), differing neuronal subtype (CA3 vs. CA1 hippocampus) and in response to Ca2+ influx, using a combination of qPCR and RNA-seq analysis. Of note, we find that the Mcu-regulating Micu gene family profile differs substantially between neurons and astrocytes, while expression of Mcu itself is markedly different between CA3 and CA1 regions in the adult hippocampus. Moreover, dynamic control of MCRG mRNA expression in response to membrane depolarization-induced Ca2+ influx is also apparent, resulting in repression of Letm1, as well as Mcu. Thus, the mRNA expression profile of MCRGs is not fixed, which may cause differences in the coupling between cytoplasmic and mitochondrial Ca2+, as well as diversity of mitochondrial Ca2+ uptake mechanisms.
钙离子摄入线粒体基质控制着细胞代谢以及存活-死亡途径。有几个基因参与控制线粒体钙离子摄入（线粒体钙调节基因，MCRGs），然而，对于影响其表达水平的因素我们了解较少。在此，我们结合定量聚合酶链反应（qPCR）和RNA测序（RNA-seq）分析，比较了不同类型神经细胞（皮层神经元与星形胶质细胞）、不同神经元亚型（海马体CA3区与CA1区）以及对钙离子内流反应中的MCRG信使核糖核酸（mRNA）表达。值得注意的是，我们发现调控线粒体钙单向转运体（Mcu）的线粒体钙摄取蛋白（Micu）基因家族特征在神经元和星形胶质细胞之间存在显著差异，而Mcu自身的表达在成年海马体的CA3区和CA1区之间也明显不同。此外，响应膜去极化诱导的钙离子内流时，MCRG mRNA表达的动态调控也很明显，导致亮氨酸拉链-EF手型跨膜蛋白1（Letm1）以及Mcu受到抑制。因此，MCRGs的mRNA表达谱并非固定不变，这可能导致细胞质与线粒体钙离子偶联的差异，以及线粒体钙离子摄取机制的多样性。
