title: A novel Drosophila mitochondrial carrier protein acts as a Mg(2+) exporter in fine-tuning mitochondrial Mg(2+) homeostasis.
abstract: The homeostasis of magnesium (Mg(2+)), an abundant divalent cation indispensable for many biological processes including mitochondrial functions, is underexplored. In yeast, the mitochondrial Mg(2+) homeostasis is accurately controlled through the combined effects of importers, Mrs2 and Lpe10, and an exporter, Mme1. However, little is known about this Mg(2+) homeostatic process in multicellular organisms. Here, we identified the first mitochondrial Mg(2+) transporter in Drosophila, the orthologue of yeast Mme1, dMme1, by homologous comparison and functional complementation. dMme1 can mediate the exportation of mitochondrial Mg(2+) when heterologously expressed in yeast. Altering the expression of dMme1, although only resulting in about a 10% change in mitochondrial Mg(2+) 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 Mg(2+)-restricted food or the dMME1-over-expressing flies the Mg(2+)-supplemented diet. Our studies therefore identified the first Drosophila mitochondrial Mg(2+) exporter, which is involved in the precise control of mitochondrial Mg(2+) homeostasis to ensure an optimal state for survival.
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: cuiyx07@gmail.com.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shanke
authors.initials: S
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Institute for Brain Disorders, Beijing, China. Electronic address: zhoubing@mail.tsinghua.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D006706:Homeostasis / Q000502:physiology*; D017136:Ion Transport / Q000502:physiology; D008274:Magnesium / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D029721:Drosophila Proteins; D024101:Mitochondrial Proteins; D008274:Magnesium
keywords: CG3476; Drosophila melanogaster; Mitochondrial Mg(2+) exporter; Mme1; Yeast; dMME1