Abstract
Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H+ export which stimulates TORC1 and liberates proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates translational bursting, liquidation of storage carbohydrates, increased ATP turnover, and the export of osmolytes. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints selected for temporal organisation that promotes oscillatory behaviour.
Highlights
Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs)
Oxygen consumption rates (OCRs) across the yeast respiratory oscillations (YROs) can be interpolated by measuring dissolved oxygen in continuous culture, where phases of higher oxygen consumption (HOC, OCR increases, DNA replication restricted) are distinguished from lower oxygen consumption (LOC) during the rest of the cycle (Fig. 1a, Supplementary Fig. 1)
We provide an experimentally derived, predictive and testable model of the YRO wherein central metabolism, signal transduction, active transport, and macromolecular condensation are temporally organized to accommodate the bioenergetic demands of protein synthesis (Figs. 3a and 5e)
Summary
Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). Saccharomyces cerevisiae undergo oscillations in oxygen consumption and many other cellular processes that synchronise spontaneously when cells are grown at high density in aerobic, nutrient-limited culture at constant pH1–3. YROs share many other key features with circadian rhythms in mammalian cells, but have shorter periods that are acutely sensitive to nutrient availability[3,4,7] For both oscillations, current understanding of the critical causal relationships and rate constants that function over the course of each cycle is inadequate to explain how the period of oscillation is determined[14]. We show that the YRO is defined by phases of higher and lower protein synthesis that drive differential rates of oxygen consumption and are facilitated by profound changes in metabolism and the intracellular ionic environment These are independent of the cell cycle. Our data support a model in which cells accumulate metabolic resources and degrade unwanted protein when translation, oxygen consumption and intracellular pH are lower, liquidate storage carbohydrates and release proteins from membrane-less compartments to support translational bursting and higher rates of respiration, when the pH is high
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