Stress response factors drive regrowth of quiescent cells

Abstract

Quiescent cells exploit an array of transcription factors to activate stress response machinery and maintain survival under nutrient-limited conditions. Our recent findings reveal that these transcription factors also play an important role in the exit of quiescence and regrowth. By studying Saccharomyces cerevisiae under a continuous, nutrient-limited condition, we found that Msn2 and Msn4 function as master regulators of glycolytic genes in the quiescent-like phase. They control the timing of transition from quiescence to growth by regulating the accumulation rate of acetyl-CoA, a key metabolite that is downstream of glycolysis and drives growth. These findings suggest a model that Msn2/4 not only protect the cells from starvation but also facilitate their regrowth from quiescence. Thus, understanding the functions of stress response transcription factors in metabolic regulation will provide deeper insight into how quiescent cells manage the capacity of regrowth.

Keywords: Acetyl-CoA; Glycolysis; Msn2; Msn4; Quiescence exit; Regrowth.

Fig. 1

Transcription factors predicted to be important in the YMC by DynaMO. The YMC trace level in the medium. The YMC is divided into three phases: OX phase represents the dissolved O₂ is red, RB phase is green and RC phase is blue. Transcription factors with binding sites enriched in each phase are listed.

Fig. 2

Model of Msn2/4-dependent glycolysis driving acetyl-CoA accumulation and regrowth of quiescent cells. In the RC quiescent phase of YMC, the yeast cells utilize the limited glucose and convert it to acetyl-CoA through Msn2/4-dependent glycolysis. Acetyl-CoA is accumulated through the RC phase and functions as a gauge/valve set that controls the transition from the RC/quiescence state to the OX/growth state.