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. 2022 May 6;23(9):5188. doi: 10.3390/ijms23095188

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Transport and regulation of intracellular iron levels. Transferrin (Tf)-bound iron is internalised through the transferrin receptor (TfR1) pathway. Inside the endosome, imported ferric iron is released and reduced to ferrous iron by Steap3. DMT1A/B-II transports ferrous iron to the cytoplasm, where it binds to PCB1/2. Cytoplasmic iron can either be stored in ferritin or incorporated into iron-dependent enzymes or the assembly of iron–sulfur cluster (ISC) scaffolds. Low levels of intracellular iron can hinder ISC assembly, thus activating the IRP1/2 iron-sensing pathways as the activity of both IRP1 and FBXL5-IRP2 is dependent on ISC availability. Activated IRP1/2 can bind to iron response elements (IREs) which regulate iron import, export and storage.