REGULATION OF IRON-METABOLISM - TRANSLATIONAL EFFECTS MEDIATED BY IRON, HEME, AND CYTOKINES

Recent advances in the knowledge of iron metabolism underscore its com plex relationship to overall cell metabolism. One of the key component s of the iron uptake and storage pathway is ferritin, a protein that s equesters iron in a nontoxic form. Ferritin synthesis is translational ly regulated by iron. Molecules such as nitric oxide and cytokines als o affect transcriptional and/or posttranscriptional ferritin synthesis . Conversely, iron-containing molecules affect expression of mitochond rial aconitase, erythroid aminolevulinic acid synthase, and nitric oxi de synthase. This observation indicates a complex linkage between iron metabolism and a variety of other important cell activities. The find ing that the cytoplasmic iron-responsive protein (IRP) has two forms a lso raises intriguing questions about the relationship between the cyt oplasmic aconitase and translational regulation of mRNAs such as ferri tin. At least one of the IRPs can be phosphorylated. These recent disc overies open exciting new avenues for research that should lead to a b etter understanding of cellular iron metabolism.