A novel Drosophila mitochondrial carrier protein acts as a Mg2Â + exporter in fine-tuning mitochondrial Mg2Â + homeostasis

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 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.