Matthias W. Hentze

Iron-sulphur clusters as genetic regulatory switches: the bifunctional iron regulatory protein-1

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.