title: Analyzing the suppression of respiratory defects in the yeast model of human mitochondrial tRNA diseases.
abstract: The respiratory defects associated with mutations in human mitochondrial tRNA genes can be mimicked in yeast, which is the only organism easily amenable to mitochondrial transformation. This approach has shown that overexpression of several nuclear genes coding for factors involved in mitochondrial protein synthesis can alleviate the respiratory defects both in yeast and in human cells. The present paper analyzes in detail the effects of overexpressed yeast and human mitochondrial translation elongation factors EF-Tu. We studied the suppressing activity versus the function in mt translation of mutated versions of this factor and we obtained indications on the mechanism of suppression. Moreover from a more extended search for suppressor genes we isolated factors which might be active in mitochondrial biogenesis. Results indicate that the multiplicity of mitochondrial factors as well as their high variability of expression levels can account for the variable severity of mitochondrial diseases and might suggest possible therapeutic approaches.
authors.affiliation: Department of Biology and Biotechnologies C. Darwin, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Montanari
authors.forename: You Fang
authors.initials: YF
authors.lastname: Zhou
authors.forename: Mario Fazzi
authors.initials: MF
authors.lastname: D'Orsi
authors.forename: Monique
authors.initials: M
authors.lastname: Bolotin-Fukuhara
authors.forename: Laura
authors.initials: L
authors.lastname: Frontali
authors.forename: Silvia
authors.initials: S
authors.lastname: Francisci
mesh_terms: D000595:Amino Acid Sequence; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D005816:Genetic Complementation Test; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption; D010444:Peptide Elongation Factor Tu / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012359:tRNA Methyltransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C489601:RIM101 protein, S cerevisiae; C485770:RRS1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C091648:TUFM protein, human; D012343:RNA, Transfer; D012359:tRNA Methyltransferases; C024845:NCL1 protein, S cerevisiae; D010444:Peptide Elongation Factor Tu; C557063:TUF1 protein, S cerevisiae
keywords: MELAS; Mitochondrial diseases; Mitochondrial protein elongation factor; NAM2; Suppressor genes; TSFM; TUF1; TUFM, genes coding for the mitochondrial protein synthesis elongation factor EF-Tu in S. cerevisiae, in H. sapiens respectively; Yeast; aa; aa-RS; amino acid(s); aminoacyl-tRNA synthetase; base-pair; bp; gene coding for the human mitochondrial translation elongation factor EF-Ts; gene coding for the yeast mitochondrial leucyl-tRNA synthetase; mitochondrial; mitochondrial encephalomyophathy, lactic acidosis, and stroke-like episodes; mt; mt DNA absent; mt DNA wild-type; rho; rho(+); tRNA mutations