Signaling pathways governing iron homeostasis in budding yeast

Iron is an essential element for eukaryotes as it participates as a redox-active co-factor in many biological processes. Since iron is also potentially toxic, iron levels are carefully regulated. In the yeast Saccharomyces cerevisiae, iron homeostasis is maintained by the transcriptional control of the iron acquisition systems (iron regulon), mainly by the iron-responsive transcriptional factors Aft1p and Yap5p. Intracellular iron is stored in the vacuole, mobilized for other locations when necessary, particularly for the mitochondria, the major site of iron-utilizing pathways. Mitochondria also play an additional role as a sensor for the regulation of cellular iron acquisition and intracellular distribution. Mounting evidence suggest that iron acquisition systems are not only responsive to iron levels but also to signaling pathways. The most recognized is the activation of the iron regulon at the diauxic shift, oppositely regulated by PKA and SNF1 kinases, major regulators of glucose signaling. Hog1p, a MAP kinase involved in stress responses, also negatively regulates iron uptake by phosphorylating Aft1p. In this review, we address organellar signaling and signal transduction pathways that play a major role in the coordination of iron homeostasis with cell growth and division.