Fig. 4.

Post-transcriptional control of iron homeostasis in neurones and glial cells. Binding of IRP1 and IRP2 to IRE in the 5′-UTR of mRNAs encoding ferritin and ferroportin represses translation, while binding of IRP1 and IRP2 to IRE in the 3′-UTR of mRNAs encoding TfR1 and DMT1 stabilises the mRNA resulting in efficient translation. In an environment of increasing oxidative stress, IRP2 is degraded while IRP1-mRNA binding is enhanced, which inhibits the synthesis of ferritin, ferroportin and APP while simultaneously upregulating the production DMT1 and TfR1. The cumulative effect of these activities is significantly increased iron