title: The Drosophila mitochondrial translation elongation factor G1 contains a nuclear localization signal and inhibits growth and DPP signaling.
abstract: Mutations in the human mitochondrial elongation factor G1 (EF-G1) are recessive lethal and cause death shortly after birth. We have isolated mutations in iconoclast (ico), which encodes the highly conserved Drosophila orthologue of EF-G1. We find that EF-G1 is essential during fly development, but its function is not required in every tissue. In contrast to null mutations, missense mutations exhibit stronger, possibly neomorphic phenotypes that lead to premature death during embryogenesis. Our experiments show that EF-G1 contains a secondary C-terminal nuclear localization signal. Expression of missense mutant forms of EF-G1 can accumulate in the nucleus and cause growth and patterning defects and animal lethality. We find that transgenes that encode mutant human EF-G1 proteins can rescue ico mutants, indicating that the underlying problem of the human disease is not just the loss of enzymatic activity. Our results are consistent with a model where EF-G1 acts as a retrograde signal from mitochondria to the nucleus to slow down cell proliferation if mitochondrial energy output is low.
authors.affiliation: Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, Florida, United States of America.
authors.forename: Catherine
authors.initials: C
authors.lastname: Trivigno
authors.forename: Theodor E
authors.initials: TE
authors.lastname: Haerry
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015536:Down-Regulation / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004625:Embryo, Nonmammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D020653:Peptide Elongation Factor G / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D010445:Peptide Elongation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D024101:Mitochondrial Proteins; D019913:Nuclear Localization Signals; D020653:Peptide Elongation Factor G; D010445:Peptide Elongation Factors; C064196:dpp protein, Drosophila; C560604:elongation factor G1, Drosophila