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.
MDI recruits translational activator Larp to the outer mitochondrial membrane to regulate mitochondrial protein expression and mtDNA replication in Drosophila ovaries.
MDI is essential for female fertility and required for the massive mtDNA replication in ovaries.
MDI localizes to the mitochondrial outer membrane and recruits the translation activator Larp onto the outer membrane.
MDI‐Larp complex boosts the synthesis of a subset of nuclear‐encoded mitochondrial proteins including mtDNA replication factors, mitochondrial ribosomal proteins, and ETC subunits.
Ectopically targeting Larp to the mitochondrial outer membrane restores mtDNA replication in ovaries and female fertility of mdi mutant flies.
- Received September 3, 2015.
- Revision received February 3, 2016.
- Accepted March 1, 2016.
- Published 2016. This article is a U.S. Government work and is in the public domain in the USA
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