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Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis.

  • O' Neill, John S
  • Hoyle, Nathaniel P
  • Robertson, J Brian
  • Edgar, Rachel S
  • Beale, Andrew D
  • Peak-Chew, Sew Y
  • Day, Jason
  • Costa, Ana SH
  • Frezza, Christian
  • Causton, Helen C
Publication Date
Sep 17, 2020
Apollo - University of Cambridge Repository
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Abstract Every aspect of yeast physiology is subject to robust temporal regulation, this becomes apparent under nutrient-limiting conditions 1-6 and results in biological oscillations whose function and mechanism is poorly resolved 7 . These yeast metabolic oscillations share features with circadian rhythms and typically interact with, but are independent of, the cell division cycle. Here we show that these cellular rhythms act to minimise energy expenditure by temporally restricting protein synthesis until sufficient cellular resources are present, whilst maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells initially ‘sequester and store’ metabolic resources such as carbohydrates, amino acids, K + and other osmolytes; which accumulate via increased synthesis, transport, autophagy and biomolecular condensation that is stimulated by low glucose and cytosolic acidification. Replete stores trigger increased H + export to elevate cytosolic pH, thereby stimulating TORC1 and liberating proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates a burst of increased protein synthesis, the liquidation of storage carbohydrates to sustain higher respiration rates and increased ATP turnover, and the export of osmolytes to maintain osmotic potential. As the duration of translational bursting is determined by cell-intrinsic factors, the period of oscillation is determined by the time cells take to store sufficient resources to license passage through the pH-dependent metabolic checkpoint that initiates translational bursting. 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 have selected for temporal organisation that promotes oscillatory behaviour.

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