A novel Drosophila mitochondrial carrier protein acts as a Mg2+ exporter in fine-tuning mitochondrial Mg2+ homeostasis
A novel Drosophila mitochondrial carrier protein acts as a Mg2+ exporter in fine-tuning mitochondrial Mg2+ homeostasis
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DOI：
10.1016/j.bbamcr.2015.10.004
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发表时间：
2016-01-01
影响因子：
5.1
通讯作者：
Zhou, Bing
中科院分区：
文献类型：
--
作者：
Cui, Yixian;Zhao, Shanke;Zhou, Bing
镁是一种丰富的二价阳离子，对包括线粒体功能在内的许多生物过程都是不可或缺的，但镁的动态平衡还没有得到充分的研究。在酵母中，线粒体镁离子的动态平衡是通过进口体mrs2和Lpe10和出口体mme1的联合作用得到精确控制的。然而，对多细胞生物体中镁离子的这种动态平衡过程知之甚少。在这里，我们通过同源比较和功能互补，鉴定了果蝇中第一个线粒体镁离子转运体，即酵母Mme1的同源基因dMme1。在酵母中异源表达时，dMme1可以介导线粒体镁离子的输出。改变dMme1的表达，虽然只导致线粒体(镁离子水平在两个方向上都只有10%的变化)，但导致果蝇的存活率显著下降。此外，通过给dMME1-RNAi果蝇饲喂镁离子受限的食物或给dMME1过度表达的果蝇添加镁离子的饲料，可以完全挽救由于dMme1基因表达变化而导致的存活率下降。因此，我们的研究确定了第一个果蝇线粒体镁离子输出器，它参与了线粒体镁离子稳态的精确控制，以确保生存的最佳状态。(C)2015爱思唯尔B.V.保留所有权利。
The homeostasis of magnesium (Mg2+), an abundant divalent cation indispensable for many biological processes including mitochondrial functions, is underexplored. In yeast, the mitochondrial Mg2+ homeostasis is accurately controlled through the combined effects of importers, Mrs2 and Lpe10, and an exporter, Mme1. However, little is known about this Mg2+ homeostatic process in multicellular organisms. Here, we identified the first mitochondrial Mg2+ transporter in Drosophila, the orthologue of yeast Mme1, dMme1, by homologous comparison and functional complementation. dMme1 can mediate the exportation of mitochondrial Mg2+ when heterologously expressed in yeast. Altering the expression of dMme1, although only resulting in about a 10% change in mitochondria( Mg2+ levels in either direction, led to a significant survival reduction in Drosophila. Furthermore, the reduced survival resulting from dMme1 expression changes could be completely rescued by feeding the dMME1-RNAi flies Mg2+-restricted food or the dMME1-over-expressing flies the Mg2+-supplemented diet. Our studies therefore identified the first Drosophila mitochondrial Mg2+ exporter, which is involved in the precise control of mitochondrial Mg2+ homeostasis to ensure an optimal state for survival. (C) 2015 Elsevier B.V. All rights reserved.