Iron speciation in the cytosol: an overview

The nature of the cytosolic iron pool remains largely uncharacterized, although a range of candidate ligands and chaperones have been proposed. Herein an overview is presented of cytosolic non heme and non iron-sulphur cluster protein iron binding sites and the influence of ligands on the redox activity of iron. This analysis leads to the concept of iron(II) glutathione functioning as the labile cytosolic iron pool and offers a means for the selection of iron over manganese in subsequent incorporation into a wide range of iron-dependent enzymes and electron transfer proteins. Glutathione and glutathione-binding glutaredoxins play a critical role in iron sulfur cluster synthesis and Fe(II)GS (iron(II) coordinated by the thiol function of glutathione) is a suitable iron donor for this biosynthetic route. Significantly, both glutathione and glutaredoxins are universally distributed and thus a controlling influence of glutathione on intracellular iron trafficking is likely to be a common feature of the majority of living organisms.