title: Molecular mechanisms of iron uptake in fungi.
abstract: Fungi, like all free-living organisms, are in competition for limiting nutrients. In accumulating iron, fungi are faced also with a trace metal whose aqueous and redox chemistry make it both relatively bio-unavailable and strongly cytotoxic. Successful adaptation to this environmental context has provided fungi with an iron uptake strategy that has three features: it relies on redox cycling to enhance iron bio-availability and reduce iron cytotoxicity; it includes both high- and low-affinity pathways that are mechanistically distinct; and it is autoregulating so as to maintain intracellular iron homeostasis. Using Saccharomyces cerevisiae as a paradigm, this review summarizes current knowledge about the four pathways by which this yeast accumulates iron. These four pathways include: siderophore iron accumulation; high affinity iron uptake via an iron permease; and two lower affinity uptake pathways through relatively non-specific divalent metal ion transporters. All of these four pathways are directly or indirectly dependent on the activity of metalloreductase activity expressed extracellularly on the plasma membrane. A variety of experimental and genomics data indicate that this resourcefulness is shared by many, if not most, fungi. On the other hand, while the autoregulation of iron metabolism in Baker's yeast is well-understood, little is known about the apparent homeostatic mechanisms in these other yeasts and fungi. The integration of these multiple uptake mechanisms and their regulation into over-all iron homeostasis in yeast concludes this brief review.
authors.affiliation: Department of Biochemistry, 140 Farber Hall, The University at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY 14214, USA. camkos@buffalo.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kosman
mesh_terms: D001203:Ascomycota / Q000378:metabolism; D001487:Basidiomycota / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002463:Cell Membrane Permeability; D002570:Ceruloplasmin / Q000378:metabolism; D038181:FMN Reductase / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005658:Fungi / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D017136:Ion Transport / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017262:Siderophores / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D017262:Siderophores; D007501:Iron; D002570:Ceruloplasmin; D038181:FMN Reductase; C023903:ferric citrate iron reductase