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Factors governing the transcriptome changes and chronological lifespan of fission yeast during phosphate starvation I

ABSTRACT: RNA-seq analysis compares gene expression of the fission yeast (Schizossacharomyces pombe) ecl123∆ mutant at various times after phosphate starvation (4, 8, 12, 24, 36 and 48h) to the ecl123∆ mutant fission yeast strain grown in phosphate replete conditions (0h, prior to phosphate starvation).

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE247922 | GEO | 2024/01/27

REPOSITORIES: GEO

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Factors governing the transcriptome changes and chronological lifespan of fission yeast during phosphate starvation

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TORC1 signaling pathway inhibition by rapamycin and caffeine affect lifespan, global gene expression and cell proliferation of fission yeast

Project description:Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 signaling pathway inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprogramming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Although rapamycin showed a much more subtle effect on global translation than did caffeine, rapamycin was more effective in prolonging chronological lifespan. Rapamycin prolonged the lifespan of non-growing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond.

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The putative ceramide-conjugation protein Cwh43 regulates G0 quiescence, nutrient metabolism and lipid homeostasis in fission yeast (Metabolome assay)

Project description:Cellular nutrient states control whether cells proliferate, or whether they enter or exit quiescence. Here, we report characterizations of fission yeast temperature-sensitive (ts) mutants of the evolutionarily conserved transmembrane protein, Cwh43, and explore its relevance to utilization of glucose, nitrogen-source, and lipids. GFP-tagged Cwh43 localizes at ER associated with the nuclear envelope and the plasma membrane, as in budding yeast. We found that cwh43 mutants failed to divide in low glucose and lost viability during quiescence under nitrogen starvation. In cwh43 mutant, comprehensive metabolome analysis demonstrated dramatic changes in marker metabolites that altered under low glucose and/or nitrogen starvation, although cwh43 apparently consumed glucose in the culture media. Furthermore, we found that cwh43 mutant had elevated levels of triacylglycerols (TGs) and coenzyme A, and that it accumulated lipid droplets. Notably, TG biosynthesis was required to maintain cell division in cwh43 mutant. Thus, Cwh43 affects utilization of glucose and nitrogen-sources, as well as storage lipid metabolism. These results may fit to a notion developed in budding yeast that Cwh43 conjugates ceramide to GPI (glycosylphosphatidylinositol)-anchored proteins and maintains integrity of membrane organization. Metabolome assay data is reported in the current study MTBLS577. Lipidome assay data associated to this study is reported in MTBLS578. Linked Studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS578' target='_blank'>MTBLS578</a>

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