Glutathione is necessary to ensure benefits of calorie restriction during ageing in Saccharomyces cerevisiae.
Calorie restriction increases longevity of mammals and yeasts but this mechanism remains unclear. In this study, the role of glutathione on lifespan extension induced by calorie restriction was investigated by using a Saccharomyces cerevisiae strain deficient in glutathione synthesis (gsh1). We observed an increase in chronological lifespan of calorie-restricted gsh1 mutant cells, compared to WT (wild type) strain, which was associated with a reduction in the levels of oxidative stress biomarkers. The gsh1 strain showed an increase in cell yield under calorie restriction that was associated with a higher pyruvate kinase activity and a reduction in oxygen consumption and aconitase activity. This indicates that the respiratory metabolism is decreased in gsh1 mutant cells. The lifespan extension of gsh1 mutant cells did not represent an advantage at long term, since old cells of gsh1 strain showed a higher frequency of petite mutants. In addition, aged WT cells outlast aged gsh1 mutant cells in direct competition assays in a fresh medium. These results suggest that glutathione is required for the beneficial effects of calorie restriction on cellular longevity.
Departamento de Bioquímica, Instituto de Química, UFRJ, 21941-909 Rio de Janeiro, RJ, Brazil. sergiocantu@iq.ufrj.br
Sérgio C
SC
Mannarino
Maria A
MA
Amorim
Marcos D
MD
Pereira
Pedro
P
Moradas-Ferreira
Anita D
AD
Panek
Vítor
V
Costa
Elis C A
EC
Eleutherio
D000154:Aconitate Hydratase / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D003470:Culture Media; D005800:Genes, Fungal; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D050050:Protein Carbonylation; D011770:Pyruvate Kinase / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D003470:Culture Media; D029701:Saccharomyces cerevisiae Proteins; D005954:Glucosephosphate Dehydrogenase; D005980:Glutathione Reductase; D011770:Pyruvate Kinase; D000154:Aconitate Hydratase; C490862:GSH1 protein, S cerevisiae; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione