Abstract
Over the past 30 years, much has been learned regarding iron homeostatic regulation in budding yeast, S. cerevisiae, including the identity of many of the proteins and molecular-level regulatory mechanisms involved. Most advances have involved inferring such mechanisms based on the analysis of iron-dysregulation phenotypes arising in various genetic mutant strains. Still lacking is a cellular- or system-level understanding of iron homeostasis. These experimental advances are summarized in this review, and a method for developing cellular-level regulatory mechanisms in yeast is presented. The method employs the results of Mössbauer spectroscopy of whole cells and organelles, iron quantification of the same, and ordinary differential equation-based mathematical models. Current models are simplistic when compared to the complexity of iron homeostasis in real cells, yet they hold promise as a useful, perhaps even required, complement to the popular genetics-based approach. The fundamental problem in comprehending cellular regulatory mechanisms is that, given the complexities involved, different molecular-level mechanisms can often give rise to virtually indistinguishable cellular phenotypes. Mathematical models cannot eliminate this problem, but they can minimize it.