Nat Rev Mol Cell Biol.: Mechanism controlling cellular and systemic iron homeostasis.

Our most recent collaborative review with several partners from the SPP 2306:

Galy B, Conrad M, Muckenthaler M.

Mechanisms controlling cellular and systemic iron homeostasis.

Galy B, Conrad M, Muckenthaler M. Nat Rev Mol Cell Biol. 2023 Oct 2. doi: 10.1038/s41580-023-00648-1. Online ahead of print. PMID: 37783783 Review.

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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