title: Mitochondrial diseases: Yeast as a model for the study of suppressors.
abstract: Mitochondrial (mt) tRNA gene mutations are an important cause of human morbidity and are associated with different syndromes. We have previously shown that the mitochondrial protein synthesis elongation factor EF-Tu and isolated sequences from the carboxy-terminal domain of yeast and human mt leucyl-tRNA synthetases (LeuRS), have a wide range of suppression capability among different yeast mt tRNA mutants having defective respiratory phenotype. Here we show that the rescuing capability can be restricted to a specific sequence of six amino acids from the carboxy-terminal domain of mt LeuRS. On the other hand by overexpressing a mutated version of mt EF-Tu in a yeast strain deleted for the endogenous nuclear gene we identified the specific region involved in suppression. Results support the possibility that a small peptide could correct defects associated with many mt tRNA mutations, suggesting a novel therapy for mitochondrial diseases treatment. The involvement of the mt EF-Tu in cellular heat stress response has also been suggested.
authors.affiliation: Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy. Electronic address: silvia.francisci@uniroma1.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Francisci
authors.affiliation: Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy; Pasteur Institute Italy - Cenci Bolognetti Foundation, Sapienza University of Rome, Viale Regina Elena, 291, 00161 Rome, Italy. Electronic address: ari.montanari@uniroma1.it.
authors.forename: Arianna
authors.initials: A
authors.lastname: Montanari
mesh_terms: D000595:Amino Acid Sequence; D015966:Gene Expression Regulation, Fungal; D016153:Genes, Suppressor; D005816:Genetic Complementation Test; D006358:Hot Temperature; D006801:Humans; D007935:Leucine-tRNA Ligase / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010444:Peptide Elongation Factor Tu / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D024101:Mitochondrial Proteins; D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer; D010444:Peptide Elongation Factor Tu; D007935:Leucine-tRNA Ligase
keywords: Mitochondrial diseases; Mitochondrial translation; Suppressor genes; Yeast; tRNA mutations