A considerable body of evidence links together mitochondrial dysfunctions, toxic action of metalloid oxyanions, and system and neurodegenerative disorders. In this study we have used the model yeast Saccharomyces cerevisiae to investigate the genetic determinants associated with tellurite resistance/sensitivity. Nitrosoguanidine-induced K₂TeO₃-resistant mutants were isolated, and one of these mutants, named Sc57-Te₅^R, was characterized. Both random spore analysis and tetrad analysis and growth of heterozygous (Te^S/Te₅^R) diploid from Sc57-Te₅^R mutant revealed that nuclear and recessive mutation(s) was responsible for the resistance. To get insight into the mechanisms responsible for K₂TeO₃-resistance, RNA microarray analyses were performed with K₂TeO₃-treated and untreated Sc57-Te₅^R cells. A total of 372 differentially expressed loci were identified corresponding to 6.37% of the S. cerevisiae transcriptome. Of these, 288 transcripts were up-regulated upon K₂TeO₃ treatment. About half of up-regulated transcripts were associated with the following molecular functions: oxidoreductase activity, structural constituent of cell wall, transporter activity. Comparative whole-genome sequencing allowed us to identify nucleotide variants distinguishing Sc57-Te₅^R from parental strain Sc57. We detected 15 CDS-inactivating mutations, and found that 3 of them affected genes coding mitochondrial ribosomal proteins (MRPL44 and NAM9) and mitochondrial ribosomal biogenesis (GEP3) pointing out to alteration of mitochondrial ribosome as main determinant of tellurite resistance.

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Journal Article | Research Support, Non-U.S. Gov't

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Pontieri P, Hartings H, Di Salvo M, Massardo DR, De Stefano M, Pizzolante G, Romano R, Troisi J, Del Giudice A, Alifano P, ... Show all

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