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.

Mitochondrial diseases: Yeast as a model for the study of suppressors / Francisci, Silvia; Montanari, Arianna. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - STAMPA. - 1864:4(2017), pp. 666-673. [10.1016/j.bbamcr.2017.01.008]

Mitochondrial diseases: Yeast as a model for the study of suppressors

FRANCISCI, Silvia;MONTANARI, Arianna
2017

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.
2017
mitochondrial diseases; mitochondrial translation; suppressor genes; tRNA mutations; yeast; molecular biology; cell biology
01 Pubblicazione su rivista::01a Articolo in rivista
Mitochondrial diseases: Yeast as a model for the study of suppressors / Francisci, Silvia; Montanari, Arianna. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - STAMPA. - 1864:4(2017), pp. 666-673. [10.1016/j.bbamcr.2017.01.008]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/959746
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