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Mechanisms controlling cellular and systemic iron homeostasis.
Galy, Bruno; Conrad, Marcus; Muckenthaler, Martina.
Afiliação
  • Galy B; German Cancer Research Center (DKFZ), Division of Virus-associated Carcinogenesis (F170), Heidelberg, Germany.
  • Conrad M; Helmholtz Zentrum München, Institute of Metabolism and Cell Death, Neuherberg, Germany.
  • Muckenthaler M; Department of Paediatric Hematology, Oncology and Immunology, University of Heidelberg, Heidelberg, Germany. Martina.Muckenthaler@med.uni-heidelberg.de.
Nat Rev Mol Cell Biol ; 25(2): 133-155, 2024 Feb.
Article em En | MEDLINE | ID: mdl-37783783
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Ferro Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Rev Mol Cell Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Ferro Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Rev Mol Cell Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha