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Verfasst von:Kitanovic, Ana [VerfasserIn]   i
 Bonowski, Felix [VerfasserIn]   i
 Heigwer, Florian [VerfasserIn]   i
 Kitanovic, Igor [VerfasserIn]   i
 Wölfl, Stefan [VerfasserIn]   i
Titel:Acetic acid treatment in S. cerevisiae creates significant energy deficiency and nutrient starvation that is dependent on the activity of the mitochondrial transcriptional complex Hap2-3-4-5
Verf.angabe:Ana Kitanovic, Felix Bonowski, Florian Heigwer, Peter Ruoff, Igor Kitanovic, Christin Ungewiss, Stefan Wölfl
E-Jahr:2012
Jahr:September 2012
Umfang:12 S.
Fussnoten:Gesehen am 04.02.2019
Titel Quelle:Enthalten in: Frontiers in oncology
Ort Quelle:Lausanne : Frontiers Media, 2011
Jahr Quelle:2012
Band/Heft Quelle:2(2012), Artikel-ID 118, Seite 1-12
ISSN Quelle:2234-943X
Abstract:Metabolic pathways play an indispensable role in supplying cellular systems with energy and molecular building blocks for growth, maintenance and repair and are tightly linked with lifespan and systems stability of cells. For optimal growth and survival cells rapidly adopt to environmental changes. Accumulation of acetic acid in stationary phase budding yeast cultures is considered to be a primary mechanism of chronological aging and induction of apoptosis in yeast, which has prompted us to investigate the dependence of acetic acid toxicity on extracellular conditions in a systematic manner. Using an automated computer controlled assay system, we investigated and model the dynamic interconnection of biomass yield- and growth rate-dependence on extracellular glucose concentration, pH conditions and acetic acid concentration. Our results show that toxic concentrations of acetic acid inhibit glucose consumption and reduce ethanol production. In absence of carbohydrates uptake, cells initiate synthesis of storage carbohydrates, trehalose and glycogen, and upregulate gluconeogenesis. Accumulation of trehalose and glycogen, and induction of gluconeogenesis depends on mitochondrial activity, investigated by depletion of the Hap2-3-4-5 complex. Analyzing the activity of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK) and glucose-6-phosphate dehydrogenase (G6PDH) we found that while high acetic acid concentration increased their activity, lower acetic acids concentrations significantly inhibited these enzymes. With this study we determined growth and functional adjustment of metabolism to acetic acid accumulation in a complex range of extracellular conditions. Our results show that substantial acidification of the intracellular environment, resulting from accumulation of dissociated acetic acid in the cytosol, is required for acetic acid toxicity, which creates a state of energy deficiency and nutrient starvation.
DOI:doi:10.3389/fonc.2012.00118
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.3389/fonc.2012.00118
 Volltext: https://www.frontiersin.org/articles/10.3389/fonc.2012.00118/full
 DOI: https://doi.org/10.3389/fonc.2012.00118
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Acetic Acid
 growth dynamic
 Hap4p
 intracellular pH homeostasis
 metabolic control
 response surface modelling
K10plus-PPN:1587203707
Verknüpfungen:→ Zeitschrift

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