Iron serves essential functions in both prokaryotes and eukaryotes, an
d cells have highly specialized mechanisms for acquiring and handling
this metal. The primary mechanism by which the concentration of iron i
n biologic systems is controlled is through the regulation of iron upt
ake. Although the role of transferrin in mammalian iron homeostasis ha
s been well characterized, the study of genetic disorders of iron meta
bolism has revealed other, transferrin-independent, mechanisms by whic
h cells can acquire iron. In an attempt to understand how eukaryotic s
ystems take up this essential element, investigators have begun studyi
ng the simple eukaryote Saccharomyces cerevisiae. Several genes have b
een identified and cloned that act in concert to allow iron acquisitio
n from the environment. Some of these genes appear to have functional
homologues in human systems. This review focuses on the recent develop
ments in understanding eukaryotic iron uptake with an emphasis on the
genetic and molecular characterization of these systems in both cultur
ed mammalian cells and S. cerevisiae. An unexpected connection between
iron and copper homeostasis has been revealed by recent genetic studi
es, which confirm biologic observations made several decades ago.