Cellular responses of Saccharomyces cerevisiae at near-zero growth rates: transcriptome analysis of anaerobic retentostat cultures

Extremely low specific growth rates (below 0.01 h-1) represent a largely unexplored area of microbial physiology. Retentostats enable controlled, energy-limited cultivation at near-zero specific growth rates while avoiding starvation. In this study, anaerobic, glucose-limited retentostats were used to analyze physiological and genome-wide transcriptional responses of Saccharomyces cerevisiae to cultivation at near-zero specific growth rates. Cultures at near-zero specific growth rates exhibited several characteristics previously associated with quiescence, including accumulation of storage polymers and an increased expression of genes involved in storage metabolism, autophagy and exit from the replicative cell cycle into G0. Analysis of transcriptome data from glucose-limited retentostat and chemostat cultures showed, as specific growth rate was decreased, quiescence-related transcriptional responses already set in at specific growth rates above 0.025 h-1. Many genes involved in mitochondrial processes were specifically upregulated at near-zero specific growth rates, possibly reflecting an increased turn-over of organelles under these conditions. Prolonged (> 2 weeks) cultivation in retentostat cultures led to induction of several genes that were previously implicated in chronological ageing. These observations stress the need for systematic dissection of physiological responses to slow growth, quiescence, ageing and starvation and indicate that controlled cultivation systems such as retentostats can contribute to this goal.

11

Boender LG, van Maris AJ, de Hulster EA, Almering MJ, van der Klei IJ, Veenhuis M, de Winde JH, Pronk JT, Daran-Lapujade P