title: Lost in transition: start-up of glycolysis yields subpopulations of nongrowing cells.
abstract: Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic changes in the abundance of glucose can undergo growth arrest. We show that this failure is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. The imbalance arises largely from the fundamental design of glycolysis, making this state of glycolysis a generic risk. Cells with unbalanced glycolysis coexisted with vital cells. Spontaneous, nongenetic metabolic variability among individual cells determines which state is reached and, consequently, which cells survive. Transient ATP (adenosine 5'-triphosphate) hydrolysis through futile cycling reduces the probability of reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.
authors.affiliation: Systems Bioinformatics/Amsterdam Institute for Molecules, Medicines and Systems (AIMMS)/Netherlands Institute for Systems Biology, VU University, De Boelelaan 1085, 1081 HV Amsterdam, Netherlands.
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Heerden
authors.forename: Meike T
authors.initials: MT
authors.lastname: Wortel
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Bruggeman
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Heijnen
authors.forename: Yves J M
authors.initials: YJ
authors.lastname: Bollen
authors.forename: Robert
authors.initials: R
authors.lastname: Planqué
authors.forename: Josephus
authors.initials: J
authors.lastname: Hulshof
authors.forename: Tom G
authors.initials: TG
authors.lastname: O'Toole
authors.forename: S Aljoscha
authors.initials: SA
authors.lastname: Wahl
authors.forename: Bas
authors.initials: B
authors.lastname: Teusink
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism*; D014199:Trehalose / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D014199:Trehalose; D005964:Glucosyltransferases; C023180:trehalose-6-phosphate synthase; D005947:Glucose