Specific biomarkers for stochastic division patterns and starvation‐induced quiescence under limited glucose levels in fission yeast

Abstract

Glucose as a source of energy is centrally important to our understanding of life. We investigated the cell division–quiescence behavior of the fission yeast Schizosaccharomyces pombe under a wide range of glucose concentrations (0–111 mm). The mode of S. pombe cell division under a microfluidic perfusion system was surprisingly normal under highly diluted glucose concentrations (5.6 mm, 1/20 of the standard medium, within human blood sugar levels). Division became stochastic, accompanied by a curious division-timing inheritance, in 2.2–4.4 mm glucose. A critical transition from division to quiescence occurred within a narrow range of concentrations (2.2–1.7 mm). Under starvation (1.1 mm) conditions, cells were mostly quiescent and only a small population of cells divided. Under fasting (0 mm) conditions, division was immediately arrested with a short chronological lifespan (16 h). When cells were first glucose starved prior to fasting, they possessed a substantially extended lifespan (∼14 days). We employed a quantitative metabolomic approach for S. pombe cell extracts, and identified specific metabolites (e.g. biotin, trehalose, ergothioneine, S-adenosyl methionine and CDP-choline), which increased or decreased at different glucose concentrations, whereas nucleotide triphosphates, such as ATP, maintained high concentrations even under starvation. Under starvation, the level of S-adenosyl methionine increased sharply, accompanied by an increase in methylated amino acids and nucleotides. Under fasting, cells rapidly lost antioxidant and energy compounds, such as glutathione and ATP, but, in fasting cells after starvation, these and other metabolites ensuring longevity remained abundant. Glucose-starved cells became resistant to 40 mm H2O2 as a result of the accumulation of antioxidant compounds.

Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose

“…46 are starved and stop dividing with high viability. 49 Consistently, when cells grown in the presence of 3% glucose were transferred to the same medium with 0.2% glucose, the Gad8 phosphorylation was unaltered (Fig. 2C).…”

“…49 We noticed, however, that the Dtor1 and Dgad8 mutant strains failed to grow under such glucose-limited conditions (Fig. 5B), indicating that active TORC2-Gad8 signaling is essential for cellular response to glucose limitation.…”

“…51 In contrast, we found that glucose deprivation does not significantly affect the abundance of the TORC2 subunits in fission yeast. The cellular ATP level in fission yeast goes down only to »80% at 30 min after a shift from 2% to 0.02% glucose, 49 a treatment that markedly reduces Gad8 phosphorylation by TORC2 within 5 min (Fig. 2C).…”

Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity

“…Earlier EGT was shown to accumulate during nutrient-limited growth of Schizosaccharomyces pombe under a wide range of glucose concentrations (0 -111 mM) (46). EGT was also found to accumulate 1 h following nitrogen starvation in S. pombe (47).…”

“…The doubling time of S. pombe is substantially shorter compared with M. tuberculosis, and thus it is plausible that EGT is required by the cell sooner and is synthesized more quickly than we observed in M. tuberculosis. Interestingly, these low glucose and nitrogen conditions in S. pombe are characterized by the cells transitioning from a dividing to a quiescent state (46,47).…”