Litsios, Athanasios

English

De celdelingscyclus - het proces waarbij twee dochtercellen worden gevormd uit één oorspronkelijke moedercel - is essentieel voor voortzetting van het leven, en fouten in de regulatie van dit proces kunnen leiden tot ziektes. Aangezien celdeling een energetisch en biosynthetisch zeer kostbaar proces is, moeten cellen nauwkeurig beslissen wanneer ze het programma van celdeling uitvoeren. Recente bevindingen toonden aan dat enkele fenotypische aspecten van microbiële cellen bepaald kunnen worden door metabole snelheden, oftewel fluxen, onafhankelijk van de extracellulaire beschikbaarheid van voedingsstoffen. Deze bevindingen inspireerden de hypothese dat de beslissing van knopvormende gist om het celdelingsproces uit te voeren afhankelijk is van metabole fluxen. Gebruikmakend van methoden op zowel enkel cel- als populatieniveau, werd gevonden dat de snelheid van de glycolyse inderdaad kan bepalen of gistcellen het celdelingsproces doorlopen, onafhankelijk van de extracellulaire beschikbaarheid van glucose. Bovendien werd gevonden dat, naast de invloed op het wel of niet plaatsvinden van celdeling, de activiteit van de stofwisseling ook belangrijk is voor de uitvoering van dit proces. Meer specifiek werd er gevonden dat, hoewel DNA replicatie grotendeels ongevoelig is voor de snelheid van de glycolyse, de ongehinderde vorming van een dochtercel een voldoende hoge flux door de glycolyse vereist. Ten slotte, in de zoektocht naar een mechanistisch verband tussen metabole snelheden en controle over de celcyclus, werd er gevonden dat de zeer dynamische snelheid van de eiwitsynthese een piek vertoont vlak voordat toewijding aan de celdelingscyclus plaatsvindt, wat leidt tot een toename in de concentratie van een belangrijke activator van de celcyclus.The cell division cycle - the process by which two daughter cells are generated from an initial mother cell - is fundamental for the continuation of life, and its dysregulation is linked to disease. Because cell division is energetically and biosynthetically a highly demanding process, cells need to carefully decide when to pursue the execution of their cell division program. Recent findings showed that several phenotypic aspects of microbial cells can be shaped by metabolic rates, or otherwise, fluxes, independently of the extracellular nutrient conditions. These findings inspired the hypothesis that the commitment of budding yeast cells to the cell division cycle is a decision that depends on metabolic flux. Combining single-cell and population-level approaches, it was found that the rate of glycolysis could dictate whether yeast cells commit to the cell division cycle or abstain from it, independently of extracellular glucose availability. Further, it was found that apart from the commitment to the cell division program, metabolic rates are also important for its execution. Specifically, it was found that while DNA replication is majorly insensitive to the rate of glycolysis, the process of bud formation requires a sufficiently high glycolytic rate for its unimpeded progression. Finally, in the quest of the mechanistic link between metabolic rate and cell cycle activation, it was found that the rate of protein synthesis, which is highly dynamic, peaks right before cell cycle commitment, causing an increase in the concentration of a critical upstream cell cycle activator

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   University of GroningenMetabolic-rate dependent cell cycle entry and progression in Saccharomyces cerevisiaeLitsios, AthanasiosIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2017Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Litsios, A. (2017). Metabolic-rate dependent cell cycle entry and progression in Saccharomyces cerevisiae.University of Groningen.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 21-06-2022Propositions -Intracellular metabolic fluxes can shape the microbial phenotype independently of changes in the extracellular environment. -The rate of glycolysis dictates whether yeast cells initiate a cell division cycle or reside to quiescence. -After its initiation, DNA replication can be completed irrespectively of external carbon availability. -The START activator Cln3 is a cyclin that cycles. -Yeast cells take important decisions on the basis of their cash holdings. -“Πάντα χωρεῖ καὶ οὐδὲν μένει”  (“Everything changes and nothing remains still”) – Heraclitus; c. 535 – c. 475 BC. -Dynamic, single-cell studies are inevitable for obtaining a systems-level understanding  of cell physiological processes and their regulation.  Metabolic-rate dependent cell cycle entry and progression in Saccharomyces cerevisiae Athanasios Litsios, Groningen 2017  

Metabolic-rate dependent cell cycle entry and progression in Saccharomyces cerevisiae

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Metabolic-rate dependent cell cycle entry and progression in Saccharomyces cerevisiae

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