Dual role of starvation signaling in promoting growth and recovery

Abstract

Growing cells are subject to cycles of nutrient depletion and repletion. A shortage of nutrients activates a starvation program that promotes growth in limiting conditions. To examine whether nutrient-deprived cells prepare also for their subsequent recovery, we followed the transcription program activated in budding yeast transferred to low-phosphate media and defined its contribution to cell growth during phosphate limitation and upon recovery. An initial transcription wave was induced by moderate phosphate depletion that did not affect cell growth. A second transcription wave followed when phosphate became growth limiting. The starvation program contributed to growth only in the second, growth-limiting phase. Notably, the early response, activated at moderate depletion, promoted recovery from starvation by increasing phosphate influx upon transfer to rich medium. Our results suggest that cells subject to nutrient depletion prepare not only for growth in the limiting conditions but also for their predicted recovery once nutrients are replenished.

A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis, to couple metabolism to cell cycle progression.

“…The PHO regulon comprises of several genes that respond to phosphate starvation, and maintains internal phosphate levels by balancing transport of Pi from the external environment, from within vacuolar stores, and the nucleus (Figure 5A) (Ljungdahl and Daignan-Fornier, 2012; Secco et al , 2012). Extensive studies have defined general cellular responses to phosphate limitation (Ogawa, DeRisi and Brown, 2000; Wykoff and O’Shea, 2001; Boer et al , 2003, 2010; Saldanha, Brauer and Botstein, 2004; Gresham et al , 2011; Levy et al , 2011; Choi et al , 2017; Gurvich, Leshkowitz and Barkai, 2017). In general, the PHO response is very sensitive to phosphate limitation, inducing rapidly to restore internal phosphate levels.…”

“…Studies have long observed that trehalose increases upon phosphate starvation (Lillie and Pringle, 1980; Klosinska et al , 2011), and TPS2 is also upregulated (Ogawa, DeRisi and Brown, 2000). In these conditions, central carbon metabolism is down, and phosphate limitation is a ‘general starvation’ cue (Brauer et al , 2008; Boer et al , 2010; Gurvich, Leshkowitz and Barkai, 2017). Why this occurs has not been immediately apparent.…”

“…These data also biochemically explain earlier observations from pathogenic fungi, which show that that the amount of trehalose synthesis determines flux through the pentose phosphate pathway, and nitrogen metabolism (Wilson et al , 2007). Additionally, a recent study observed that phosphate starvation results in not just better cell survival in limited nutrient conditions, but also promotes efficient recovery when the nutrients become available (Gurvich, Leshkowitz and Barkai, 2017). Since trehalose accumulation and utilization is tightly coupled with exit and re-entry into cell division cycle respectively (Shi et al , 2010; Shi and Tu, 2013), we propose that trehalose synthesis during phosphate-limitation has dual roles.…”

Autotoxin-mediated voluntary triage in starved yeast community

“…In a crisis, such as starvation, organisms should adapt at both individual (1,2) and population levels (3)(4)(5). In unicellular organisms, the former has been intensively studied as an adaptation phenomenon (11)(12)(13), whereas the latter is poorly understood. Severe conditions decrease the carrying capacity (6), and unicellular organisms have to decrease the population size (7,8).…”

Gene transcription as a limiting factor in protein production and cell growth

“…The molecular or mechanistic basis of these limitations, however, remained unclear. Gene expression signature is a sensitive probe of internal limitations; Budding yeast experiencing amino acids limitation, for example, induce GCN4-target genes (Gasch et al, 2000; Tamari et al, 2014), while cells depleted of internal phosphate induce PHO4 targets (Gurvich et al, 2017; Gutteridge et al, 2010). Both responses are gradual, providing a quantitative readout of the limitation.…”