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Galy, B.* ; Conrad, M. ; Muckenthaler, M.*

Mechanisms controlling cellular and systemic iron homeostasis.

Nat. Rev. Mol. Cell Biol. 25, 133–155 (2024)
DOI PMC
In mammals, hundreds of proteins use iron in a multitude of cellular functions, including vital processes such as mitochondrial respiration, gene regulation and DNA synthesis or repair. Highly orchestrated regulatory systems control cellular and systemic iron fluxes ensuring sufficient iron delivery to target proteins is maintained, while limiting its potentially deleterious effects in iron-mediated oxidative cell damage and ferroptosis. In this Review, we discuss how cells acquire, traffick and export iron and how stored iron is mobilized for iron–sulfur cluster and haem biogenesis. Furthermore, we describe how these cellular processes are fine-tuned by the combination of various sensory and regulatory systems, such as the iron-regulatory protein (IRP)–iron-responsive element (IRE) network, the nuclear receptor co-activator 4 (NCOA4)-mediated ferritinophagy pathway, the prolyl hydroxylase domain (PHD)–hypoxia-inducible factor (HIF) axis or the nuclear factor erythroid 2-related factor 2 (NRF2) regulatory hub. We further describe how these pathways interact with systemic iron homeostasis control through the hepcidin–ferroportin axis to ensure appropriate iron fluxes. This knowledge is key for the identification of novel therapeutic opportunities to prevent diseases of cellular and/or systemic iron mismanagement.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Transferrin Receptor 1; Regulatory Proteins; Responsive Element; Mouse Model; H-ferritin; Hepcidin Expression; Messenger-rna; Hemochromatosis Proteins; Mitochondrial Ferritin; Targeted Deletion
ISSN (print) / ISBN 1471-0072
e-ISSN 1471-0080
Journal Nature Reviews - Molecular Cell Biology
Quellenangaben Volume: 25, Issue: , Pages: 133–155 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
Grants
European Research Council under the European Union
Else Kroner-Fresenius-Stiftung
Deutscher Akademischer Austauschdienst
Dietmar Hopp-Stiftung
Federal Ministry of Education and Research (BMBF)
Deutsche Forschungsgemeinschaft (DFG)