title: The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication.
abstract: Early embryonic development features rapid nuclear DNA replication cycles, but lacks mtDNA replication. To meet the high-energy demands of embryogenesis, mature oocytes are furnished with vast amounts of mitochondria and mtDNA However, the cellular machinery driving massive mtDNA replication in ovaries remains unknown. Here, we describe a Drosophila AKAP protein, MDI that recruits a translation stimulator, La-related protein (Larp), to the mitochondrial outer membrane in ovaries. The MDI-Larp complex promotes the synthesis of a subset of nuclear-encoded mitochondrial proteins by cytosolic ribosomes on the mitochondrial surface. MDI-Larp's targets include mtDNA replication factors, mitochondrial ribosomal proteins, and electron-transport chain subunits. Lack of MDI abolishes mtDNA replication in ovaries, which leads to mtDNA deficiency in mature eggs. Targeting Larp to the mitochondrial outer membrane independently of MDI restores local protein synthesis and rescues the phenotypes of mdi mutant flies. Our work suggests that a selective translational boost by the MDI-Larp complex on the outer mitochondrial membrane might be essential for mtDNA replication and mitochondrial biogenesis during oogenesis.
authors.affiliation: Laboratory of Molecular Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Proteomics Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Proteomics Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Gucek
authors.affiliation: Laboratory of Molecular Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA hong.xu@nih.gov.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D014176:Protein Biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D029721:Drosophila Proteins; C485865:Larp protein, Drosophila; D024101:Mitochondrial Proteins; D014157:Transcription Factors
keywords: DNA replication; oogenesis; protein synthesis