title: Can yeast be used to study mitochondrial diseases? Biolistic tRNA mutants for the analysis of mechanisms and suppressors.
abstract: Base substitutions equivalent to those causing human pathologies have been introduced in yeast mitochondrial tRNA genes. These mutants can be utilized as flexible tools to investigate the molecular aspects of mitochondrial diseases and identify correcting genes. We show that for all studied tRNA mutations (including an homoplasmic one in tRNA(Val)) the severity of phenotypes follows the same trend in four different nuclear backgrounds. Correcting genes include TUF1 and genes encoding aminoacyl-tRNA synthetase. The effect of suppressors was analyzed by Northern blot. Mutated leucyl-tRNA synthetase with highly reduced catalytic activity maintains full suppressing effect, thus suggesting a chaperone-like and/or stabilizing function.
authors.affiliation: Department of Cell and Developmental Biology, Pasteur Institute-Fondazione Cenci Bolognetti, University Sapienza, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: De Luca
authors.forename: YouFang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Arianna
authors.initials: A
authors.lastname: Montanari
authors.forename: Veronica
authors.initials: V
authors.lastname: Morea
authors.forename: Romina
authors.initials: R
authors.lastname: Oliva
authors.forename: Celine
authors.initials: C
authors.lastname: Besagni
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: D001483:Base Sequence; D019470:Biolistics / Q000379:methods*; D015152:Blotting, Northern; D006801:Humans; D050296:Microbial Viability; D028361:Mitochondrial Diseases / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D012343:RNA, Transfer / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013489:Suppression, Genetic
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer