A novel Drosophila mitochondrial carrier protein acts as a Mg2+ exporter in fine-tuning mitochondrial Mg2+ homeostasis

AbstractThe 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 mitochondrial 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