Metabolic Regulation of Quiescence Entry and Exit in Saccharomyces cerevisiae
MetadataShow full item record
Unicellular microorganisms often enter a state called quiescence when they encounter harsh environmental conditions. They stop growth and proliferation until conditions improve. In quiescence, the budding yeast slows down transcription three- to five-fold, while its translation rate drops to 0.3% of that in growth phase. Importantly, yeast quiescent cells have remarkably higher stress resistance than growing cells. Once conditions improve, they readily re-enter the cell cycle. Though quiescence is an important phase of cell life, its understanding has been limited. Previously, Allen et al. reported the isolation of quiescent yeast cells from stationary phase culture by cell density fractionation (Allen et al., 2006). Cells of high density, which they termed quiescent cells, were more stress-resistant and had more growth potential when conditions improved. However, it remained unknown how quiescent cells became dense and what mechanism allowed cells to enter quiescence. I report the intracellular glycogen and trehalose accumulation leads to increased density of quiescent yeast cells. Glycogen and trehalose are two carbon reserves yeast cells accumulate during entry into quiescence. Cells unable to produce glycogen and trehalose exhibit no density change during the entry of quiescence. Furthermore, yeast cells lacking trehalose dramatically slowed down the adaptation and growth in fresh nutrients. Thus, trehalose is a key determinant of the quiescent state and possibly fuels rapid cell cycle progression in the presence of fresh nutrients. When conditions improve, quiescent yeast cells readily re-enter growth. The proper regulation of quiescence exit in response to the environment is of vital importance to balance cell growth and quiescence. In budding yeast, CLN3 is one of the G1 cyclins that govern cell cycle entry and transition from G1 to S phase. CLN3 is the first activated G1 cyclin that subsequently induces the other G1 cyclins. Notably, CLN3 deletion slows down yeast cell cycle entry. Thus, studying CLN3 expression in response to nutrients may reveal the key mechanism of quiescence exit. I report acetyl-CoA induces immediate CLN3 transcription in quiescent yeast cells. Acetate derived surge of acetyl-CoA promotes extensive histone H3 acetylation at CLN3 promoter mediated by the SAGA complex, a histone H3 acetyltransferase. The acetylated histones loosen the chromatin at CLN3 promoter and facilitate rapid CLN3 transcription. Thus, acetyl-CoA is sensed by the SAGA complex to induce CLN3 transcription that promotes quiescence exit and regrowth. Altogether, my studies have revealed insights into how yeast cells enter and exit quiescence metabolically. In addition to yeast cell quiescence regulation, my studies may also aid in understanding the key mechanisms of quiescence regulation in higher eukaryotic systems.