ArticleBlood2021
RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 125 citations in OpenAlex.
- DDR1 sustains ferroptosis resistance in pancreatic ductal adenocarcinoma via SLC40A1-mediated iron homeostasis.Oncogene · 2026Article
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Ferroptosis in T cells: mechanisms, biology and translational opportunities.Nature reviews. Immunology · 2026Review
- MDM2 Alters Cellular Iron Homeostasis by Promoting the Degradation of Proteins Involved in Iron Storage and Iron Export.Current issues in molecular biology · 2026Article
- Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.Biomolecules · 2026Review
- Iron overload in the tumor microenvironment induces CD8Nature communications · 2026Article
- Human umbilical cord-derived mesenchymal stem cell exosomes ameliorate hepatocyte ferroptosis and sepsis-associated liver injury by restoring iron homeostasis in hepatocytes.Journal of nanobiotechnology · 2026Article
- NOX1/4 drives hepatic iron and lipid dysregulation, redox imbalance, and inflammation in ethanol-fed mice.Scientific reports · 2026Article
- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- TET1 as a master regulator controlling GPX4-dependent and -independent ferroptosis surveillance in acute myeloid leukemia.Nature communications · 2026Article
- Iron-dependent ferroptosis in cardiac microvascular endothelial cells: a key link between dysregulated iron homeostasis and microcirculatory injury during myocardial ischemia-reperfusion.Frontiers in cardiovascular medicine · 2026Review
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- Targeting hepcidin to restore oral iron efficacy after vertical sleeve gastrectomy.Frontiers in nutrition · 2026Article
- Ferroptosis and Alzheimer's disease: unraveling the molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- High intestinal iron absorption induced by decreased hepcidin leads to imbalance of iron metabolism in aging mice.Biogerontology · 2025Article
- High intestinal iron absorption induced by decreased hepcidin leads to imbalance of iron metabolism in aging mice.Biogerontology · 2025Article
- Hologenomic analysis of rectal mucus sampling for detection of adenomatous polyps and colorectal cancer.Nature communications · 2025Article
- Mechanism and regulation of iron absorption throughout the life cycle.Journal of advanced research · 2025Review
- Regulation of iron metabolism in ferroptosis: From mechanism research to clinical translation.Journal of pharmaceutical analysis · 2025Review
- Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroportin (FPN), the body's sole iron exporter, is essential for maintaining systemic iron homeostasis. In response to either increased iron or inflammation, hepatocyte-secreted hepcidin binds to FPN, inducing its internalization and subsequent degradation. However, the E3 ubiquitin ligase that underlies FPN degradation has not been identified. Here, we report the identification and characterization of a novel mechanism involving the RNF217-mediated degradation of FPN. A combination of 2 different E3 screens revealed that the Rnf217 gene is a target of Tet1, mediating the ubiquitination and subsequent degradation of FPN. Interestingly, loss of Tet1 expression causes an accumulation of FPN and an impaired response to iron overload, manifested by increased iron accumulation in the liver together with decreased iron in the spleen and duodenum. Moreover, we found that the degradation and ubiquitination of FPN could be attenuated by mutating RNF217. Finally, using 2 conditional knockout mouse lines, we found that knocking out Rnf217 in macrophages increases splenic iron export by stabilizing FPN, whereas knocking out Rnf217 in intestinal cells appears to increase iron absorption. These findings suggest that the Tet1-RNF217-FPN axis regulates iron homeostasis, revealing new therapeutic targets for FPN-related diseases.
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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.