title: Extreme calorie restriction and energy source starvation in Saccharomyces cerevisiae represent distinct physiological states.
abstract: Cultivation methods used to investigate microbial calorie restriction often result in carbon and energy starvation. This study aims to dissect cellular responses to calorie restriction and starvation in Saccharomyces cerevisiae by using retentostat cultivation. In retentostats, cells are continuously supplied with a small, constant carbon and energy supply, sufficient for maintenance of cellular viability and integrity but insufficient for growth. When glucose-limited retentostats cultivated under extreme calorie restriction were subjected to glucose starvation, calorie-restricted and glucose-starved cells were found to share characteristics such as increased heat-shock tolerance and expression of quiescence-related genes. However, they also displayed strikingly different features. While calorie-restricted yeast cultures remained metabolically active and viable for prolonged periods of time, glucose starvation resulted in rapid consumption of reserve carbohydrates, population heterogeneity due to appearance of senescent cells and, ultimately, loss of viability. Moreover, during starvation, calculated rates of ATP synthesis from reserve carbohydrates were 2-3 orders of magnitude lower than steady-state ATP-turnover rates calculated under extreme calorie restriction in retentostats. Stringent reduction of ATP turnover during glucose starvation was accompanied by a strong down-regulation of genes involved in protein synthesis. These results demonstrate that extreme calorie restriction and carbon starvation represent different physiological states in S. cerevisiae.
authors.affiliation: Kluyver Centre for Genomics of Industrial Fermentation, Julianalaan 67, 2628 BC Delft, The Netherlands; Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands.
authors.forename: Léonie G M
authors.initials: LG
authors.lastname: Boender
authors.forename: Marinka J H
authors.initials: MJ
authors.lastname: Almering
authors.forename: Madelon
authors.initials: M
authors.lastname: Dijk
authors.forename: Antonius J A
authors.initials: AJ
authors.lastname: van Maris
authors.forename: Johannes H
authors.initials: JH
authors.lastname: de Winde
authors.forename: Jack T
authors.initials: JT
authors.lastname: Pronk
authors.forename: Pascale
authors.initials: P
authors.lastname: Daran-Lapujade
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D031204:Caloric Restriction; D015536:Down-Regulation; D004736:Energy-Generating Resources; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D018869:Heat-Shock Response; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013217:Starvation
chemical_list: D015415:Biomarkers; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D005947:Glucose