IRPIREMechanismen

IRPIREMechanismen refers to the post-transcriptional regulation of cellular iron metabolism by iron regulatory proteins (IRP1 and IRP2) interacting with iron-responsive elements (IREs) in target mRNAs. This regulatory framework coordinates iron uptake, storage, and utilization by controlling the stability and translation of a subset of transcripts, most notably ferritin and the transferrin receptor.

The core mechanism centers on IRPs binding to IREs, which are conserved hairpin structures located in the untranslated regions of specific mRNAs. When IRPs bind to IREs in the 5' untranslated region, translation initiation is repressed (for example, ferritin mRNA). When they bind to IREs in the 3' untranslated region, mRNA stability is increased (for example, transferrin receptor 1 mRNA). Through these interactions, cells adjust ferritin synthesis and iron uptake in response to iron availability.

Regulation of IRP activity depends on cellular iron status. IRP1 can exist as an iron-sulfur cluster-containing cytosolic aconitase or as an RNA-binding apo-form; under iron-replete conditions, IRP1 largely adopts the aconitase form and does not bind IREs. IRP2 lacks aconitase activity and is regulated primarily by iron-dependent degradation, mediated by the E3 ligase FBXL5. Low iron stabilizes and activates IRPs, promoting high iron uptake and reduced storage; high iron reduces IRP binding, limiting uptake and increasing storage.

Physiological significance includes maintenance of systemic and cellular iron homeostasis, with implications for erythropoiesis, immunity, and metabolic processes. Dysregulation of IRP-IRE mechanisms has been linked to anemia of inflammation, iron overload disorders, and certain cancers and neurodegenerative conditions. Further research continues to elucidate tissue-specific roles and therapeutic potential.