Iron-sulfur cluster signaling: The common thread in fungal iron regulation

Iron homeostasis in fungi involves balancing iron uptake and storage with iron utilization to achieve adequate, nontoxic levels of this essential nutrient. Extensive work in the nonpathogenic yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe has uncovered unique iron regulation networks for each organism that control iron metabolism via distinct molecular mechanisms. However, common themes have emerged from these studies. The activities of all fungal iron-sensing transcription factors characterized to date are regulated via iron-sulfur cluster signaling. Furthermore, glutaredoxins often play a key role in relaying the intracellular iron status to these DNA-binding proteins. Recent work with fungal pathogens, including Candida and Aspergillus species and Cryptococcus neoformans, has revealed novel iron regulation mechanisms, yet similar roles for iron-sulfur clusters and glutaredoxins in iron signaling have been confirmed. This review will focus on these recent discoveries regarding iron regulation pathways in both pathogenic and nonpathogenic fungi.