To divide or not to divide: a key role of Rim15 in calorie-restricted yeast cultures.
The PAS kinase Rim15 is proposed to integrate signals from different nutrient-sensing pathways and to control transcriptional reprogramming of Saccharomyces cerevisiae upon nutrient depletion. Despite this proposed role, previous transcriptome analyses of rim15 mutants solely focused on growing cultures. In the present work, retentostat cultivation enabled analysis of the role of Rim15 under severely calorie-restricted, virtually non-growing conditions. Under these conditions, deletion of RIM15 affected transcription of over 10-fold more genes than in growing cultures. Transcriptional responses, metabolic rates and cellular morphology indicated a key role of Rim15 in controlled cell-cycle arrest upon nutrient depletion. Moreover, deletion of rim15 reduced heat-shock tolerance in non-growing, but not in growing cultures. The failure of rim15 cells to adapt to calorie restriction by entering a robust post-mitotic state resembles cancer cell physiology and shows that retentostat cultivation of yeast strains can provide relevant models for healthy post-mitotic and transformed human cells.
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands; Kluyver Centre for Genomics of Industrial Fermentation, PO Box 5057, 2600 GA Delft, The Netherlands.
Markus M M
MM
Bisschops
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands; Kluyver Centre for Genomics of Industrial Fermentation, PO Box 5057, 2600 GA Delft, The Netherlands.
Priscilla
P
Zwartjens
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands; Kluyver Centre for Genomics of Industrial Fermentation, PO Box 5057, 2600 GA Delft, The Netherlands.
Sebastiaan G F
SG
Keuter
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands; Kluyver Centre for Genomics of Industrial Fermentation, PO Box 5057, 2600 GA Delft, The Netherlands.
Jack T
JT
Pronk
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands; Kluyver Centre for Genomics of Industrial Fermentation, PO Box 5057, 2600 GA Delft, The Netherlands. Electronic address: p.a.s.daran-lapujade@tudelft.nl.
Pascale
P
Daran-Lapujade
D031204:Caloric Restriction; D003470:Culture Media; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*
D003470:Culture Media; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C410736:Rim15 protein, S cerevisiae
Calorie restriction; Cell cycle; Retentostat; Rim15; Robustness; Saccharomyces cerevisiae