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Review
. 2004 Jun;68(2):187-206.
doi: 10.1128/MMBR.68.2.187-206.2004.

"Sleeping beauty": quiescence in Saccharomyces cerevisiae

Joseph V Gray  1 , Gregory A Petsko, Gerald C Johnston, Dagmar Ringe, Richard A Singer, Margaret Werner-Washburne
Affiliations
Review

"Sleeping beauty": quiescence in Saccharomyces cerevisiae

Joseph V Gray et al. Microbiol Mol Biol Rev. 2004 Jun.

Abstract

The cells of organisms as diverse as bacteria and humans can enter stable, nonproliferating quiescent states. Quiescent cells of eukaryotic and prokaryotic microorganisms can survive for long periods without nutrients. This alternative state of cells is still poorly understood, yet much benefit is to be gained by understanding it both scientifically and with reference to human health. Here, we review our knowledge of one "model" quiescent cell population, in cultures of yeast grown to stationary phase in rich media. We outline the importance of understanding quiescence, summarize the properties of quiescent yeast cells, and clarify some definitions of the state. We propose that the processes by which a cell enters into, maintains viability in, and exits from quiescence are best viewed as an environmentally triggered cycle: the cell quiescence cycle. We synthesize what is known about the mechanisms by which yeast cells enter into quiescence, including the possible roles of the protein kinase A, TOR, protein kinase C, and Snf1p pathways. We also discuss selected mechanisms by which quiescent cells maintain viability, including metabolism, protein modification, and redox homeostasis. Finally, we outline what is known about the process by which cells exit from quiescence when nutrients again become available.

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Figures

FIG. 1.
FIG. 1.
Relationship between the state of a culture of yeast cells growing to saturation in rich medium (YPD) and the state of the constituent cells. When yeast cells are inoculated into rich medium containing glucose, the cells proliferate rapidly using fermentation and the density of the culture (reflected in optical density at 600 nm [OD600]) increases logarithmically with time (log phase). When glucose is consumed in the culture at the diauxic shift (after approximately 1 day), the cells cease rapid cell proliferation and readjust their metabolism from fermentation to respiration to utilize other carbon sources present in the medium. In the resulting post-diauxic shift state of the culture, constituent cells proliferate very slowly. When external carbon sources are exhausted, the culture reaches saturation (at approximately 5 to 7 days postinoculation) and the constituent cells cease proliferation and enter the quiescent state.
FIG. 2.
FIG. 2.
The cell quiescence cycle and its relationship to the cell division cycle. The cell quiescence cycle is the process by which nutrient limitation (e.g., carbon starvation in our reference case) causes exit from active proliferation (the cell division cycle) and triggers entry into the stable nonproliferating state, quiescence/G(0). Only after a favorable change in nutrient availability will a turn of the quiescence cycle be completed, since nutrient availability triggers exit from quiescence/G(0). The cell quiescence cycle and the cell division cycle intersect at the G1 phase, where a cell has not yet committed to the cell division cycle. In the presence of sufficient nutrients and with no other influences, a G1 cell will pass START, after which it is committed to completing a turn of the cell division cycle with production of a daughter cell. Slow depletion of an essential nutrient such as carbon will allow the completion of an ongoing cell division cycle but will not allow passage through START. In this case of insufficient nutrient availability, the cell will enter the cell quiescence cycle.
FIG. 3.
FIG. 3.
Summary of the known signaling pathways thought to control aspects of entry into quiescence. The TOR and PKA pathways are active in the presence of nutrients and act to repress aspects of quiescence. When cells are starved of carbon, both pathways are downregulated. Inactivation of the TORs causes activation (albeit transiently) of PKC, leading to some characteristics of quiescence such as a remodeled cell wall. The Snf1 pathway is inhibited by the presence of fermentable carbon sources such as glucose. When such sources are depleted, Snf1 is activated and contributes to the switch from fermentative to respiratory metabolism that is essential for entry into quiescence.
FIG. 4.
FIG. 4.
Cell transitions that occur when a culture is grown to saturation cell density. As shown in Fig. 1, as a culture of cells is grown to stationary phase, two distinct and temporally separated transitions occur with concomitant transitions of the constituent cells. At the diauxic shift transition of the culture, cells switch from fermentation to respiration and from rapid proliferation to slow proliferation. The trigger for this transition is thought to be exhaustion of a fermentable carbon source. At this transition, the PKA and TOR pathways are downregulated and the PKC and Snf1 pathways are activated, the former only transiently. At saturation of the culture, cells switch from a slowly proliferating and respiring state to a quiescent state/G(0) that is also thought to be respiring. The trigger for this transition is thought to be depletion of nonfermentable carbon sources in the medium, i.e., carbon starvation. Mediators of this latter transition are not known, nor has a role for the PKA, TOR, PKA, or Snf1 pathways been established.
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References

    1. Ashrafi, K., T. A. Farazi, and J. I. Gordon. 1998. A role for Saccharomyces cerevisiae fatty acid activation protein 4 in regulating protein N-myristoylation during entry into stationary phase. J. Biol. Chem. 273:25864-25874. - PubMed
    1. Ashrafi, K., D. Sinclair, J. I. Gordon, and L. Guarente. 1999. Passage through stationary phase advances replicative aging in Saccharomyces cerevisiae. Proc. Nat. Acad. Sci. USA 96:9100-9105. - PMC - PubMed
    1. Barbet, N. C., U. Schneider, S. B. Helliwell, I. Stansfield, M. F. Tuite, and M. N. Hall. 1996. TOR controls translation initiation and early G1 progression in yeast. Mol. Biol. Cell 7:25-42. - PMC - PubMed
    1. Beck, T., and M. N. Hall. 1999. The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402:689-692. - PubMed
    1. Benaroudj, N., D. H. Lee, and A. L. Goldberg. 2001. Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J. Biol. Chem. 276:24261-24267. - PubMed

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