RESUMEN
Yeast is a suitable model system to analyze the mechanism of lifespan. In this study, to identify novel factors involved in chronological lifespan, we isolated a mutant with a long chronological lifespan and found a missense mutation in the sur2+ gene, which encodes a homolog of Saccharomyces cerevisiae sphingolipid C4-hydroxylase in fission yeast. Characterization of the mutant revealed that loss of sur2 function resulted in an extended chronological lifespan. The effect of caloric restriction, a well-known signal for extending lifespan, is thought to be dependent on the sur2+ gene.
Asunto(s)
Oxigenasas de Función Mixta/genética , Oxidorreductasas/genética , Proteínas de Schizosaccharomyces pombe/genética , Schizosaccharomyces/fisiología , Viabilidad Microbiana , Mutación , Fenotipo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Esfingolípidos/análisisRESUMEN
In the longevity research by using yeasts, chronological lifespan is defined as the survival time after entry into stationary phase. Previously, screening for long lived mutants of Schizosaccharomyces pombe was performed to identify the novel factors involved in longevity. From this screening, one long lived mutant called as No.36 was obtained. In this study, we identified the mutation caused in gas1+, which encodes glucanosyltransferase (gas1-287 mutation) is responsible for the longevity of No.36 mutant. Through the analysis of this mutant, we found that cell wall perturbing agent micafungin also extends chronological lifespan in fission yeast. This lifespan extension depended on both Pmk1 and Sty1 MAP kinases, and longevity caused by the gas1-287 mutation also depended on these kinases. In summary, we propose that the gas1-287 mutation causes longevity as the similar mechanism as cell wall stress depending on Pmk1 and Sty1 MAPK pathways.
Asunto(s)
Longevidad/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutación , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/genética , Pared Celular/metabolismo , Genes FúngicosRESUMEN
Chronological lifespan is defined by how long a cell can survive in a non-dividing state. In yeast, it is measured by viability after entry into the stationary phase. To understand the regulatory mechanisms of chronological lifespan in Schizosaccharomyces pombe, it is necessary to identify and characterize novel factors involved in the regulation of chronological lifespan. To this end, we have screened for a long-lived mutant and identified that novel gene nnk1+ that encodes an essential protein kinase is the determinant of chronological lifespan. We showed that the expression of major glucose transporter gene, ght5+, is decreased in the isolated nnk1-35 mutant, suggesting that Nnk1 protein is involved in the regulation of ght5+ The consumption of glucose in the growth medium after saturated growth was lower in the nnk1-35 mutant than that in wild-type cell. The isolated ght5 deletion mutant showed long-lived phenotype. Based on these results, we propose that Nnk1 regulates chronological lifespan through the regulation of ght5+ Nnk1 might coordinate glucose availability and lifespan in fission yeast.
