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dc.contributor.authorO' Neill, John Sen
dc.contributor.authorHoyle, Nathaniel Pen
dc.contributor.authorRobertson, J Brianen
dc.contributor.authorEdgar, Rachel Sen
dc.contributor.authorBeale, Andrew Den
dc.contributor.authorPeak-Chew, Sew Yen
dc.contributor.authorDay, Jasonen
dc.contributor.authorCosta, Ana SHen
dc.contributor.authorFrezza, Christianen
dc.contributor.authorCauston, Helen Cen
dc.date.accessioned2020-10-05T23:31:25Z
dc.date.available2020-10-05T23:31:25Z
dc.date.issued2020-09-17en
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311112
dc.description.abstractAbstract 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.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherSpringer Nature
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectRibosomesen
dc.subjectEukaryotic Cellsen
dc.subjectYeastsen
dc.subjectOxygenen
dc.subjectGlycogenen
dc.subjectIonomycinen
dc.subjectMolecular Chaperonesen
dc.subjectProteomeen
dc.subjectBioreactorsen
dc.subjectProteomicsen
dc.subjectProtein Biosynthesisen
dc.subjectProtein Processing, Post-Translationalen
dc.subjectEnergy Metabolismen
dc.subjectCircadian Rhythmen
dc.subjectHeat-Shock Responseen
dc.subjectOsmolar Concentrationen
dc.subjectOsmotic Pressureen
dc.subjectAutophagyen
dc.subjectMetabolomicsen
dc.subjectProteostasisen
dc.subjectMechanistic Target of Rapamycin Complex 1en
dc.titleEukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2020en
prism.publicationNameNature communicationsen
prism.startingPage4706
prism.volume11en
dc.identifier.doi10.17863/CAM.58201
dcterms.dateAccepted2020-08-13en
rioxxterms.versionofrecord10.1038/s41467-020-18330-xen
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-09-17en
dc.contributor.orcidO' Neill, John S [0000-0003-2204-6096]
dc.contributor.orcidHoyle, Nathaniel P [0000-0002-3250-0494]
dc.contributor.orcidBeale, Andrew D [0000-0002-2051-0919]
dc.contributor.orcidPeak-Chew, Sew Y [0000-0002-7602-6384]
dc.contributor.orcidCosta, Ana SH [0000-0001-8932-6370]
dc.contributor.orcidFrezza, Christian [0000-0002-3293-7397]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMedical Research Council (MC_UU_12022/6)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International