The mitochondrial outer membrane protein MDI promotes local protein synthesis and mt DNA replication

Early embryonic development features rapid nuclear DNA replication cycles, but lacks mt DNA replication. To meet the high‐energy demands of embryogenesis, mature oocytes are furnished with vast amounts of mitochondria and mt DNA . However, the cellular machinery driving massive mt DNA 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 mt DNA replication factors, mitochondrial ribosomal proteins, and electron‐transport chain subunits. Lack of MDI abolishes mt DNA replication in ovaries, which leads to mt DNA 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 mt DNA replication and mitochondrial biogenesis during oogenesis.