TY - JOUR T1 - An Integrative Model of Ion Regulation in Yeast A1 - Ke, Ruian A1 - Ingram, Piers J. A1 - Haynes, Ken Y1 - 2013/01/17 N2 - Author Summary Ion regulation is fundamental to cell physiology. The concentrations of monovalent ions, such as H+, K+ and Na+, determine many physiological parameters such as cell volume, plasma membrane potential and intracellular pH. In yeast cells, these parameters are maintained within a narrow range during the adaptation to external perturbations, including ionic, osmotic and alkaline pH stress. This is achieved by the remarkably coordinated activities of ion transporters, regulatory molecules and signaling pathways. The response characteristics of individual components in adaptation have been studied extensively. However, a coherent understanding of the coordinated adaptation process is lacking. In this study, we address this gap by constructing a mathematical model that integrates the characteristics of the ion transporters, regulatory molecules, signaling pathways and changes in cell volume. Using this model, we characterize the impact of ionic, osmotic and alkaline pH stresses on cellular physiology and analyze the role that individual components play in the cellular adaptation processes. Our results also reveal system level properties achieved by the concerted regulatory responses. Therefore, this integrated model serves as a suitable tool to understand the coordinated processes of ion regulation in response to environmental stresses, and to make predictions that are experimentally testable. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 9 IS - 1 UR - https://doi.org/10.1371/journal.pcbi.1002879 SP - e1002879 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002879 ER -