Regulation of genes of iron metabolism by the iron-response proteins

Iron is an essential nutrient, yet excess iron can be toxic to cells. The u ptake of iron by mammalian cells is post-transcriptionally regulated by the interaction of iron-response proteins (IRP1 and IRP2) with iron-response e lements (IREs) found in the mRNAs of genes of iron metabolism, such as ferr itin, the transferrin receptor, erythroid aminolevulinic acid synthase, and mitochondrial aconitase. The IRPs are RNA binding proteins that bind to th e IRE (found in the mRNAs of the regulated genes) in an iron- dependent man ner. Binding of IRPs to the IREs leads to changes in the expression of the regulated genes and subsequent changes in the uptake, utilization, or stora ge of intracellular iron. Recent work has demonstrated that the binding of the IRPs to the IREs can also be modulated by changes in the redox state or oxidative stress level of the cell. These findings provide an important li nk between iron metabolism and states of oxidative stress.