ArticleProceedings of the National Academy of Sciences of the United States of America2002
The hemochromatosis protein HFE inhibits iron export from macrophages.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 127 citations in OpenAlex.
- Higher iron stores and the HFE 187C>G variant delay onset of peripheral neuropathy during combination antiretroviral therapy.PloS one · 2020Trial
- Polymer-mRNA complexes for monocyte-trafficked, lymph node-targeted cancer vaccination.Nature biomedical engineering · 2026Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Whole exome sequencing reveal 83 novel Mendelian disorders carrier P/LP variants in Chinese adult patients.Journal of human genetics · 2023Article
- Liver Iron Loading in Alcohol-Associated Liver Disease.The American journal of pathology · 2023Review
- Understanding How Minerals Contribute to Optimal Immune Function.Journal of immunology research · 2023Review
- Severe anaemia, iron deficiency, and susceptibility to invasive bacterial infections.Wellcome open research · 2023Review
- Investigation of the effects of overexpression of jumping translocation breakpoint (JTB) protein in MCF7 cells for potential use as a biomarker in breast cancer.American journal of cancer research · 2022Article
- Cell-specific expression ofHaematologica · 2021Article
- An HIV elite controller patient carrying the homozygous H63D variant in the homeostatic iron regulator gene: A case report.Medicine · 2021Article
- HFE inhibits type I IFNs signaling by targeting the SQSTM1-mediated MAVS autophagic degradation.Autophagy · 2021Article
- Iron Availability in Tissue Microenvironment: The Key Role of Ferroportin.International journal of molecular sciences · 2021Review
- Classical and intermediate monocytes scavenge non-transferrin-bound iron and damaged erythrocytes.JCI insight · 2019Article
- Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.Nature communications · 2018Article
- Haemochromatosis.Nature reviews. Disease primers · 2018Review
- The role of HFE genotype in macrophage phenotype.Journal of neuroinflammation · 2018Article
- Genetic and Dietary Iron Overload Differentially Affect the Course ofFrontiers in cellular and infection microbiology · 2017Article
- Iron homeostasis: a new job for macrophages in adipose tissue?Trends in endocrinology and metabolism: TEM · 2015Review
- Molecular basis of HFE-hemochromatosis.Frontiers in pharmacology · 2014Review
- HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease.Frontiers in pharmacology · 2014Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary hemochromatosis (HH) is a disorder of iron metabolism caused by common mutations in the gene HFE. The HFE protein binds to transferrin receptor-1 (TfR1) in competition with transferrin, and in vitro, reduces cellular iron by reducing iron uptake. However, in vivo, HFE is strongly expressed by liver macrophages and intestinal crypt cells, which behave as though they are relatively iron-deficient in HH. These latter observations suggest, paradoxically, that expression of wild-type HFE may lead to iron accumulation in these specialized cell types. Here we show that wild-type HFE protein raises cellular iron by inhibiting iron efflux from the monocytemacrophage cell line THP-1, and extend these results to macrophages derived from healthy individuals and HH patients. In addition, we find that the HH-associated mutant H41D has lost the ability to inhibit iron release despite binding to TfR1 as well as wild-type HFE. Finally, we show that the ability of HFE to block iron release is not competitively inhibited by transferrin. We conclude that HFE has two mutually exclusive functions, binding to TfR1 in competition with Tf, or inhibition of iron release.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.