title: An Essential Role for COPI in mRNA Localization to Mitochondria and Mitochondrial Function.
abstract: Nuclear-encoded mRNAs encoding mitochondrial proteins (mMPs) can localize directly to the mitochondrial surface, yet how mMPs target mitochondria and whether RNA targeting contributes to protein import into mitochondria and cellular metabolism are unknown. Here, we show that the COPI vesicle coat complex is necessary for mMP localization to mitochondria and mitochondrial function. COPI inactivation leads to reduced mMP binding to COPI itself, resulting in the dissociation of mMPs from mitochondria, a reduction in mitochondrial membrane potential, a decrease in protein import in vivo and in vitro, and severe deficiencies in mitochondrial respiration. Using a model mMP (OXA1), we observed that COPI inactivation (or mutation of the potential COPI-interaction site) led to altered mRNA localization and impaired cellular respiration. Overall, COPI-mediated mMP targeting is critical for mitochondrial protein import and function, and transcript delivery to the mitochondria or endoplasmic reticulum is regulated by cis-acting RNA sequences and trans-acting proteins.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Zabezhinsky
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Slobodin
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, Hoppe-Seyler-Strasse 4, 72076 Tuebingen, Germany.
authors.forename: Doron
authors.initials: D
authors.lastname: Rapaport
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: jeffrey.gerst@weizmann.ac.il.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gerst
mesh_terms: D019069:Cell Respiration; D020755:Coat Protein Complex I / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D020755:Coat Protein Complex I; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C090858:OXA1 protein; D021122:Protein Subunits; D012333:RNA, Messenger; D003576:Electron Transport Complex IV