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Título: | Coiled coil domain-containing protein 56 (CCDC56) is a novel mitochondrial protein essential for cytochrome c oxidase function |
Autor: | Peralta, Susana; Clemente, Paula; Sánchez-Martínez, Álvaro; Calleja, Manuel CSIC; Hernández-Sierra, Rosana CSIC; Matsushima, Yuichi; Adán, Cristina CSIC; Ugalde, Cristina; Fernández-Moreno, Miguel Ángel CSIC ORCID; Kaguni, Laurie S. CSIC; Garesse, Rafael CSIC ORCID | Fecha de publicación: | 2012 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | Journal of Biological Chemistry 287(29): 24174-24185 (2012) | Resumen: | In Drosophila melanogaster, the mitochondrial transcription factor B1 (d-mtTFB1) transcript contains in its 5′-untranslated region a conserved upstream open reading frame denoted as CG42630 in FlyBase. We demonstrate that CG42630 encodes a novel protein, the coiled coil domain-containing protein 56 (CCDC56), conserved in metazoans. We show that Drosophila CCDC56 protein localizes to mitochondria and contains 87 amino acids in flies and 106 in humans with the two proteins sharing 42% amino acid identity. We show by rapid amplification of cDNA ends and Northern blotting that Drosophila CCDC56 protein and mtTFB1 are encoded on a bona fide bicistronic transcript. We report the generation and characterization of two ccdc56 knock-out lines in Drosophila carrying the ccdc56 D6 and ccdc56 D11 alleles. Lack of the CCDC56 protein in flies induces a developmental delay and 100% lethality by arrest of larval development at the third instar. ccdc56 knock-out larvae show a significant decrease in the level of fully assembled cytochrome c oxidase (COX) and in its activity, suggesting a defect in complex assembly; the activity of the other oxidative phosphorylation complexes remained either unaffected or increased in the ccdc56 knock-out larvae. The lethal phenotype and the decrease in COX were partially rescued by reintroduction of a wild-type UAS-ccdc56 transgene. These results indicate an important role for CCDC56 in the oxidative phosphorylation system and in particular in COX function required for proper development in D. melanogaster. Wepropose CCDC56 as a candidate factor required for COX biogenesis/assembly. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. | URI: | http://hdl.handle.net/10261/76594 | DOI: | 10.1074/jbc.M112.343764 | Identificadores: | doi: 10.1074/jbc.M112.343764 issn: 0021-9258 e-issn: 1083-351X |
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