ArticleHaematologica2022
UBA6 and NDFIP1 regulate the degradation of ferroportin.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Novel loci and biomedical consequences of iron homoeostasis variation.Communications biology · 2024Pooled it
- Amyloid Precursor Protein Abnormalities Destabilize Membrane Ferroportin: A Novel Mechanism Underlying Early Brain Pathologies and Memory Impairment in Alzheimer's Disease.International journal of molecular sciences · 2026Article
- Low NDFIP1-driven metabolic alterations in CD8 + T cells: implications for immune evasion and therapy resistance in HNSC.Cancer cell international · 2026Article
- Modulation of hepcidin synthesis: the core link in the bi-directional relationship between iron and obesity.Reviews in endocrine & metabolic disorders · 2026Review
- Multidimensional iron dysmetabolism and gut-brain axis interactions in restless legs syndrome: from peripheral deficiency to central dysregulation.Frontiers in aging neuroscience · 2026Review
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Mechanism and regulation of iron absorption throughout the life cycle.Journal of advanced research · 2025Review
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- PTEN: a new dawn in Parkinson's disease treatment.Frontiers in cellular neuroscience · 2025Review
- Article
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application.Frontiers in pharmacology · 2024Review
- Cross-species comparison illuminates the importance of iron homeostasis for splenic anti-immunosenescence.Aging cell · 2023Article
- Membrane Transporters Involved in Iron Trafficking: Physiological and Pathological Aspects.Biomolecules · 2023Review
- ARIH1 inhibits influenza A virus replication and facilitates RIG-I dependent immune signaling by interacting with SQSTM1/p62.Virology journal · 2023Article
- Molecular Mechanisms of Iron and Heme Metabolism.Annual review of nutrition · 2022Review
- HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.Expert review of hematology · 2022Article
- Dapagliflozin Ameliorates Renal Tubular Ferroptosis in Diabetes via SLC40A1 Stabilization.Oxidative medicine and cellular longevity · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepcidin regulates iron homeostasis by controlling the level of ferroportin, the only membrane channel that facilitates export of iron from within cells. Binding of hepcidin to ferroportin induces the ubiquitination of ferroportin at multiple lysine residues and subsequently causes the internalization and degradation of the ligand-channel complex within lysosomes. The objective of this study was to identify components of the ubiquitin system that are involved in ferroportin degradation. A HepG2 cell line, which inducibly expresses ferroportingreen fluorescent protein (FPN-GFP), was established to test the ability of small interfering (siRNA) directed against components of the ubiquitin system to prevent BMP6- and exogenous hepcidin-induced ferroportin degradation. Of the 88 siRNA directed against components of the ubiquitin pathway that were tested, siRNA-mediated depletion of the alternative E1 enzyme UBA6 as well as the adaptor protein NDFIP1 prevented BMP6- and hepcidin-induced degradation of ferroportin in vitro. A third component of the ubiquitin pathway, ARIH1, indirectly inhibited ferroportin degradation by impairing BMP6-mediated induction of hepcidin. In mice, the AAV-mediated silencing of Ndfip1 in the murine liver increased the level of hepatic ferroportin and increased circulating iron. The results suggest that the E1 enzyme UBA6 and the adaptor protein NDFIP1 are involved in iron homeostasis by regulating the degradation of ferroportin. These specific components of the ubiquitin system may be promising targets for the treatment of iron-related diseases, including iron overload and anemia of inflammation.
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Registered trials
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.