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dc.contributor.authorDikicioglu, Duygu
dc.contributor.authorDereli Eke, Elif
dc.contributor.authorEraslan, Serpil
dc.contributor.authorOliver, Stephen
dc.contributor.authorKirdar, Betul
dc.date.accessioned2018-12-19T00:31:19Z
dc.date.available2018-12-19T00:31:19Z
dc.date.issued2018-11-20
dc.identifier.issn1478-811X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287187
dc.description.abstractBACKGROUND: Rapamycin is a potent inhibitor of the highly conserved TOR kinase, the nutrient-sensitive controller of growth and aging. It has been utilised as a chemotherapeutic agent due to its anti-proliferative properties and as an immunosuppressive drug, and is also known to extend lifespan in a range of eukaryotes from yeast to mammals. However, the mechanisms through which eukaryotic cells adapt to sustained exposure to rapamycin have not yet been thoroughly investigated. METHODS: Here, S. cerevisiae response to long-term rapamycin exposure was investigated by identifying the physiological, transcriptomic and metabolic differences observed for yeast populations inoculated into low-dose rapamycin-containing environment. The effect of oxygen availability and acidity of extracellular environment on this response was further deliberated by controlling or monitoring the dissolved oxygen level and pH of the culture. RESULTS: Yeast populations grown in the presence of rapamycin reached higher cell densities complemented by an increase in their chronological lifespan, and these physiological adaptations were associated with a rewiring of the amino acid metabolism, particularly that of arginine. The ability to synthesise amino acids emerges as the key factor leading to the major mechanistic differences between mammalian and microbial TOR signalling pathways in relation to nutrient recognition. CONCLUSION: Oxygen levels and extracellular acidity of the culture were observed to conjointly affect yeast populations, virtually acting as coupled physiological effectors; cells were best adapted when maximal oxygenation of the culture was maintained in slightly acidic pH, any deviation necessitated more extensive readjustment to additional stress factors.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSaccharomyces cerevisiae
dc.subjectOxygen
dc.subjectSirolimus
dc.subjectAmino Acids
dc.subjectAdaptation, Physiological
dc.subjectTranscription, Genetic
dc.subjectDose-Response Relationship, Drug
dc.subjectTime Factors
dc.titleSaccharomyces cerevisiae adapted to grow in the presence of low-dose rapamycin exhibit altered amino acid metabolism.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameCell Commun Signal
prism.startingPage85
prism.volume16
dc.identifier.doi10.17863/CAM.34496
dcterms.dateAccepted2018-11-08
rioxxterms.versionofrecord10.1186/s12964-018-0298-y
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11-20
dc.contributor.orcidDikicioglu, Duygu [0000-0002-3018-4790]
dc.contributor.orcidOliver, Stephen [0000-0001-6330-7526]
dc.identifier.eissn1478-811X
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-11-20


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