Metabolic cycling without cell division cycling in respiring yeast. Proc Natl Acad Sci USA

Departments of Biology and Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2011; 108(47):19090-5. DOI: 10.1073/pnas.1116998108
Source: PubMed


Despite rapid progress in characterizing the yeast metabolic cycle, its connection to the cell division cycle (CDC) has remained unclear. We discovered that a prototrophic batch culture of budding yeast, growing in a phosphate-limited ethanol medium, synchronizes spontaneously and goes through multiple metabolic cycles, whereas the fraction of cells in the G1/G0 phase of the CDC increases monotonically from 90 to 99%. This demonstrates that metabolic cycling does not require cell division cycling and that metabolic synchrony does not require carbon-source limitation. More than 3,000 genes, including most genes annotated to the CDC, were expressed periodically in our batch culture, albeit a mere 10% of the cells divided asynchronously; only a smaller subset of CDC genes correlated with cell division. These results suggest that the yeast metabolic cycle reflects a growth cycle during G1/G0 and explains our previous puzzling observation that genes annotated to the CDC increase in expression at slow growth.

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    • "In the long-period YMC, a single cell alternates between periods of high (oxidative (OX) phase) or low oxygen consumption (reductive building (RB) and charging (RC) phases), the residence time in each phase being nutrient-dependent. For exponentially growing cells in batch culture, the majority of cells in the population will be in the OX phase of the YMC (Slavov et al., 2011). Transcript levels for genes that cycle in the YMC will change as the cell moves through these phases; at any time, some cells in an asynchronous population will contain a transcript and some will not. "
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    • "With the development of new technologies (such as microfluidics systems with a mass sensor), precise monitoring of cell size has become possible (Son et al. 2012). Considering the ongoing systems biology research on cell growth (Ferrezuelo et al. 2012) and metabolism (Slavov et al. 2011), a better understanding of the interplay between cell growth and division can be expected in the near future. The systems approach can also be used to address epigenetic factors. "
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    • "Such a decrease in NADPH production could explain at least in part the decreased stress resistance that we measured (Figures 3D and 3E). This pathway for THF-mediated mitochondrial NADPH production is transcriptional upregulated with the growth rate and increased respiration of yeast growing on ethanol carbon source (Slavov and Botstein, 2011), suggesting its broader significance for respiratory metabolism. "
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