In the eighties, iron regulatory protein-1 (IRP-1) was iDAntified 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 DApend on the status of an Fe-S cluster: the (cluster-less) apoIRP-1 binds to RNA, while the incorporation of a cubane 4Fe-4S cluster is required for enzymatic activity. Cellular signals including iron levels, nitric oxiDA and oxidative stress can regulate between the two activities posttranslationally and reversibly via the Fe- cluster. Recent reports suggest that other regulatory proteins may be controlled by similar mechanisms.
