Molecular mechanisms of iron uptake in eukaryotes

Iron serves essential functions in both prokaryotes and eukaryotes, and cells have highly specialized mechanisms for acquiring and handling this metal. The primary mechanism by which the concentration of iron in biologic systems is controlled is through the regulation of iron uptake. Although the role of transferrin in mammalian iron homeostasis has been well characterized, the study of genetic disorders of iron metabolism has revealed other, transferrin-independent, mechanisms by which cells can acquire iron. In an attempt to understand how eukaryotic systems take up this essential element, investigators have begun studying the simple eukaryote Saccharomyces cerevisiae. Several genes have been identified and cloned that act in concert to allow iron acquisition from the environment. Some of these genes appear to have functional homologues in human systems. This review focuses on the recent developments in understanding eukaryotic iron uptake with an emphasis on the genetic and molecular characterization of these systems in both cultured mammalian cells and S. cerevisiae. An unexpected connection between iron and copper homeostasis has been revealed by recent genetic studies, which confirm biologic observations made several decades ago.