A tps1Δ persister-like state in Saccharomyces cerevisiae is regulated by MKT1

PLoS One. 2020 May 29;15(5):e0233779. doi: 10.1371/journal.pone.0233779. eCollection 2020.

Abstract

Trehalose metabolism in yeast has been linked to a variety of phenotypes, including heat resistance, desiccation tolerance, carbon-source utilization, and sporulation. The relationships among the several phenotypes of mutants unable to synthesize trehalose are not understood, even though the pathway is highly conserved. One of these phenotypes is that tps1Δ strains cannot reportedly grow on media containing glucose or fructose, even when another carbon source they can use (e.g. galactose) is present. Here we corroborate the recent observation that a small fraction of yeast tps1Δ cells do grow on glucose, unlike the majority of the population. This is not due to a genetic alteration, but instead resembles the persister phenotype documented in many microorganisms and cancer cells undergoing lethal stress. We extend these observations to show that this phenomenon is glucose-specific, as it does not occur on another highly fermented carbon source, fructose. We further demonstrate that this phenomenon appears to be related to mitochondrial complex III function, but unrelated to inorganic phosphate levels in the cell, as had previously been suggested. Finally, we found that this phenomenon is specific to S288C-derived strains, and is the consequence of a variant in the MKT1 gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Electron Transport Complex III / metabolism
  • Fermentation
  • Fructose / metabolism
  • Glucose / metabolism*
  • Glucosyltransferases / genetics
  • Loss of Function Mutation
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / physiology*
  • Trehalose / biosynthesis

Substances

  • MKT1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Fructose
  • Trehalose
  • Glucosyltransferases
  • trehalose-6-phosphate synthase
  • Electron Transport Complex III
  • Glucose

Grants and funding

This research was supported by the National Institute of General Medical Sciences Center for Quantitative Biology to DB (GM071508), National Institutes of Health grant to DB (GM046406), Department of Energy grant to JR (DE-SC0012461), National Institutes of Health grant to PG (GM097852), and Calico Life Sciences LLC. Calico Life Sciences LLC provided support in the form of salaries for authors PAG, DGH, RSM, and DB. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.