The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication Mitochondrial localization of a Tom20‐LarpGFP (Tom20‐Larp)

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The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication Mitochondrial localization of a Tom20‐LarpGFP (Tom20‐Larp) fusion protein in an mdi1 egg chamber stained with ATP‐S to reveal mitochondria. Scale bars, 20 μm. Hatching rates and mtDNA contents of eggs produced by flies with different genotypes relative to wt control; each data point represents the mean of three independent replicates. Error bars represent SD. Expression of Tom20‐Larp in mdi1 (mdi1; Tom20‐Larp) significantly restored the mtDNA level and hatching rate. N = 3 × >100 eggs/genotype for hatching rate. The relative mtDNA level was the average of three biological repeats. P‐values of comparing mdi1; Tom20‐Larp to mdi1: for mtDNA level, P = 0.0209; for hatching rate, P = 3.4758E−05. Model of the role of MDI and Larp in mitochondrial biogenesis. MDI (green rectangle) localizes at the mitochondrial outer membrane and recruits Larp (blue rectangle) to the mitochondrial surface. Larp interacts with polysome (blobs) and translation stimulators and stimulates the translation of a subset of nuclear‐encoded mRNAs. Proteins synthesized on the mitochondrial surface are in close vicinity of the Tom–Tim mitochondrial transporter complexes, which would facilitate their rapid transport into the matrix. The targets of MDI‐Larp complexes include most nuclear‐encoded ETC subunits, mitochondrial ribosomal proteins, TFAM, and mtDNA polymerase (Tamas) (collectively represented in red). Mitochondrial ribosomes are required for the biogenesis of proteins encoded by mtDNA, all of which are ETC subunits. Thus, MDI‐Larp complex seem to coordinate the expression of both nuclear and mitochondrial genome to promote the biogenesis of ETC complexes. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. EMBO J, Volume: 35, Issue: 10, Pages: 1045-1057, First published: 06 April 2016, DOI: (10.15252/embj.201592994)