Regulatory and pathogenic mechanisms in response to iron deficiency and excess in fungi

Iron is an essential element for all eukaryote organisms because of its redox properties, which are important for many biological processes such as DNA synthesis, mitochondrial respiration, oxygen transport, lipid, and carbon metabolism. For this reason, living organisms have developed different strategies and mechanisms to optimally regulate iron acquisition, transport, storage, and uptake in different environmental responses. Moreover, iron plays an essential role during microbial infections. Saccharomyces cerevisiae has been of key importance for decrypting iron homeostasis and regulation mechanisms in eukaryotes. Specifically, the transcription factors Aft1/Aft2 and Yap5 regulate the expression of genes to control iron metabolism in response to its deficiency or excess, adapting to the cell's iron requirements and its availability in the environment. We also review which iron-related virulence factors have the most common fungal human pathogens (Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans). These factors are essential for adaptation in different host niches during pathogenesis, including different fungal-specific iron-uptake mechanisms. While being necessary for virulence, they provide hope for developing novel antifungal treatments, which are currently scarce and usually toxic for patients. In this review, we provide a compilation of the current knowledge about the metabolic response to iron deficiency and excess in fungi.