Potassium starvation in yeast: mechanisms of homeostasis revealed by mathematical modeling.
The intrinsic ability of cells to adapt to a wide range of environmental conditions is a fundamental process required for survival. Potassium is the most abundant cation in living cells and is required for essential cellular processes, including the regulation of cell volume, pH and protein synthesis. Yeast cells can grow from low micromolar to molar potassium concentrations and utilize sophisticated control mechanisms to keep the internal potassium concentration in a viable range. We developed a mathematical model for Saccharomyces cerevisiae to explore the complex interplay between biophysical forces and molecular regulation facilitating potassium homeostasis. By using a novel inference method ("the reverse tracking algorithm") we predicted and then verified experimentally that the main regulators under conditions of potassium starvation are proton fluxes responding to changes of potassium concentrations. In contrast to the prevailing view, we show that regulation of the main potassium transport systems (Trk1,2 and Nha1) in the plasma membrane is not sufficient to achieve homeostasis.
Department of Mathematics and Technology, RheinAhrCampus, University of Applied Sciences, Koblenz, Remagen, Germany.
Matthias
M
Kahm
Clara
C
Navarrete
Vicent
V
Llopis-Torregrosa
Rito
R
Herrera
Lina
L
Barreto
Lynne
L
Yenush
Joaquin
J
Ariño
Jose
J
Ramos
Maik
M
Kschischo
D000465:Algorithms; D027682:Cation Transport Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019295:Computational Biology; D003198:Computer Simulation; D005800:Genes, Fungal; D006706:Homeostasis; D017136:Ion Transport; D008954:Models, Biological; D009154:Mutation; D011188:Potassium / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D027682:Cation Transport Proteins; C000631624:NHA1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017923:Sodium-Hydrogen Exchangers; C085258:TRK2 protein, S cerevisiae; C068664:TRK1 protein, S cerevisiae; C092477:PMA1 protein, S cerevisiae; D006180:Proton-Translocating ATPases; D011188:Potassium