ArticleJournal of biomedical science2023
Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation.
Article in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 22 citations in OpenAlex.
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- Reimagining the contribution of iron in Parkinson's disease.Neurobiology of disease · 2026Review
- Cerebrospinal Fluid from Restless Legs Syndrome Patients Reduces Iron Uptake in Blood-Brain Barrier Endothelial Cells by Disrupting the Regulation of Transferrin Receptors.Annals of neurology · 2026Article
- Clinical implications of ferroptosis in critical illness: a narrative review.Journal of intensive care · 2026Review
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- L-DOPA influences transferrin-dependent iron release at the blood-brain barrier.Fluids and barriers of the CNS · 2026Article
- Extracellular vesicles released from blood-brain barrier endothelial cells mediate brain iron accumulation during LPS-induced brain inflammation.The Journal of biological chemistry · 2026Article
- Ferroptosis in Myocardial Fibrosis: Mechanisms and Therapeutic Insights.Antioxidants (Basel, Switzerland) · 2026Review
- Multidimensional iron dysmetabolism and gut-brain axis interactions in restless legs syndrome: from peripheral deficiency to central dysregulation.Frontiers in aging neuroscience · 2026Review
- Systemic iron availability differentially shapes tumor and brain iron handling in a sex-dependent manner in glioblastoma.PloS one · 2026Article
- Multi-omics identify hallmark protein and lipid features of small extracellular vesicles circulating in human plasma.Nature cell biology · 2025Article
- Ferroptosis: a new target for depression prevention and treatment.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Ovotransferrin as a Multifunctional Bioactive Protein: Unlocking Its Potential in Animal Health and Wellness.Veterinary sciences · 2025Review
- Iron Metabolism and Muscle Aging: Where Ferritinophagy Meets Mitochondrial Quality Control.Cells · 2025Review
- Functional Characterization of the Hephaestin Variant D568H Provides Novel Mechanistic Insights on Iron-Dependent Asbestos-Induced Carcinogenesis.International journal of molecular sciences · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- The Ferroxidase-Permease System for Transport of Iron Across Membranes: From Yeast to Humans.International journal of molecular sciences · 2025Review
- The role of ferroptosis-related non-coding RNA in liver fibrosis.Frontiers in cell and developmental biology · 2024Review
- Amyloid-β exposed astrocytes induce iron transport from endothelial cells at the blood-brain barrier by altering the ratio of apo- and holo-transferrin.Journal of neurochemistry · 2023Article
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5 authors at 2 institutions in 1 country.
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Abstract
backgroundApo- (iron free) and holo- (iron bound) transferrin (Tf) participate in precise regulation of brain iron uptake at endothelial cells of the blood-brain barrier. Apo-Tf indicates an iron-deficient environment and stimulates iron release, while holo-Tf indicates an iron sufficient environment and suppresses additional iron release. Free iron is exported through ferroportin, with hephaestin as an aid to the process. Until now, the molecular mechanisms of apo- and holo-Tf influence on iron release was largely unknown.
methodsHere we use a variety of cell culture techniques, including co-immunoprecipitation and proximity ligation assay, in iPSC-derived endothelial cells and HEK 293 cells to investigate the mechanism by which apo- and holo-Tf influence cellular iron release. Given the established role of hepcidin in regulating cellular iron release, we further explored the relationship of hepcidin to transferrin in this model.
resultsWe demonstrate that holo-Tf induces the internalization of ferroportin through the established ferroportin degradation pathway. Furthermore, holo-Tf directly interacts with ferroportin, whereas apo-Tf directly interacts with hephaestin. Only pathophysiological levels of hepcidin disrupt the interaction between holo-Tf and ferroportin, but similar hepcidin levels are unable to interfere with the interaction between apo-Tf and hephaestin. The disruption of the holo-Tf and ferroportin interaction by hepcidin is due to hepcidin's ability to more rapidly internalize ferroportin compared to holo-Tf.
conclusionsThese novel findings provide a molecular mechanism for apo- and holo-Tf regulation of iron release from endothelial cells. They further demonstrate how hepcidin impacts these protein-protein interactions, and offer a model for how holo-Tf and hepcidin cooperate to suppress iron release. These results expand on our previous reports on mechanisms mediating regulation of brain iron uptake to provide a more thorough understanding of the regulatory mechanisms mediating cellular iron release in general.
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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.