Extreme calorie restriction in yeast retentostats induces uniform non-quiescent growth arrest

Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):231-242. doi: 10.1016/j.bbamcr.2016.11.002. Epub 2016 Nov 4.


Non-dividing Saccharomyces cerevisiae cultures are highly relevant for fundamental and applied studies. However, cultivation conditions in which non-dividing cells retain substantial metabolic activity are lacking. Unlike stationary-phase (SP) batch cultures, the current experimental paradigm for non-dividing yeast cultures, cultivation under extreme calorie restriction (ECR) in retentostat enables non-dividing yeast cells to retain substantial metabolic activity and to prevent rapid cellular deterioration. Distribution of F-actin structures and single-cell copy numbers of specific transcripts revealed that cultivation under ECR yields highly homogeneous cultures, in contrast to SP cultures that differentiate into quiescent and non-quiescent subpopulations. Combined with previous physiological studies, these results indicate that yeast cells subjected to ECR survive in an extended G1 phase. This study demonstrates that yeast cells exposed to ECR differ from carbon-starved cells and offer a promising experimental model for studying non-dividing, metabolically active, and robust eukaryotic cells.

Keywords: Actin structure; Extreme calorie restriction; Heterogeneity; Non-dividing; Retentostat; mRNA FISH.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Batch Cell Culture Techniques
  • Bioreactors
  • Cell Cycle Checkpoints / genetics*
  • Culture Media / chemistry
  • Energy Metabolism / genetics*
  • Gene Expression Regulation, Fungal*
  • Glucose / deficiency*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism


  • Actins
  • Culture Media
  • HSP12 protein, S cerevisiae
  • HSP26 protein, S cerevisiae
  • Heat-Shock Proteins
  • Saccharomyces cerevisiae Proteins
  • Glucose