IRON-SULFUR CLUSTERS AS GENETIC REGULATORY SWITCHES - THE BIFUNCTIONAL IRON REGULATORY PROTEIN-1

In the eighties, iron regulatory protein-1 (IRP-1) was identified as a cytoplasmic mRNA-binding protein that regulates vertebrate cell iron metabolism. More recently, IRP-1 was found to represent the functional cytoplasmic homologue of mitochondrial aconitase, a citric acid cycle enzyme. Its two functions are mutually exclusive and depend on the st atus of an Fe-S cluster: the (cluster-less) apoIRP-1 binds to RNA, whi le the incorporation of a cubane 4Fe-4S cluster is required for enzyma tic activity. Cellular signals including iron levels, nitric oxide and oxidative stress can regulate between the two activities posttranslat ionally and reversibly via the EPS cluster, Recent reports suggest tha t other regulatory proteins may be controlled by similar mechanisms.