Iron regulatory factor — the conductor of cellular iron regulation

Abstract

All cells have to adjust uptake, utilization and storage of iron according to the availability and their requirement for this essential metal. Progress in recent years has led to the elucidation of the molecular control mechanisms that co-ordinate the uptake, utilization and storage of iron in mammalian cells and has highlighted the role of a newly-identified regulatory protein, the iron regulatory factor (IRF). IRF is a cytoplasmic protein that senses the intracellular iron level and responds by adjusting its function. When the iron level is low, it binds to so-called ‘iron responsive elements’ (IREs) contained in the mRNAs encoding proteins involved in iron metabolism and erythroid haem synthesis. When levels of cellular iron rise, IRF converts into the enzyme aconitase and looses its ability to bind to IREs. We discuss both functions of this Janus face protein and describe how its function is controlled by the status of an iron sulphur cluster in the IRF protein. We also speculate about how an IRF-mediated regulation may relate to certain medical disorders.