ArticleBlood2021
CD63 is regulated by iron via the IRE-IRP system and is important for ferritin secretion by extracellular vesicles.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 144 citations in OpenAlex.
- The role of iron in normal and impaired testicular function.Andrology · 2026Review
- Surface protein profiling reveals depot-specific features of subcutaneous and visceral adipose progenitor cells.Biochemistry and biophysics reports · 2026Article
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- Ferritin Associates with Interspecific Variation in Iron Accumulation among Five Economically Important Bivalves: Sequence, Expression, and Functional Analyses.Biological trace element research · 2026Article
- Iron Salts, but Not Iron Oxide Nanoparticles, Drive High-Yield Production of Iron-Engineered Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- 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
- Targeting macrophage ferritin heavy chain mitigates ferroptosis and lung injury in experimental acute respiratory distress syndrome.Nature communications · 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
- Tumor-associated macrophages promote ferroptosis resistance in glioblastoma by stimulating iron-loaded extracellular vesicle release.Journal of neuro-oncology · 2026Article
- Article
- Targeted deletion of macrophage ferritin heavy chain protects from macrophage ferroptosis in acute respiratory distress syndrome.Research square · 2026Article
- Ferroptosis in smoke inhalation injury: from mechanisms to potential therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Exosome Augmentation Technologies for Drug Delivery and Disease Treatment: A Review.Biomaterials research · 2026Review
- Iron-related intercellular communication in the liver: Main players and mechanisms.European journal of clinical investigation · 2026Review
- The D826V point mutation inFrontiers in cell and developmental biology · 2026Article
- Atosiban-conjugated 3WJ-pRNA nanoparticles delivering GAS1-enhanced extracellular vesicles: targeting the decidua to combat recurrent miscarriage.Journal of nanobiotechnology · 2025Article
- Ferroptosis and cancer: when iron turns against tumors.Cellular and molecular life sciences : CMLS · 2025Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular vesicles (EVs) transfer functional molecules between cells. CD63 is a widely recognized EV marker that contributes to EV secretion from cells. However, the regulation of its expression remains largely unknown. Ferritin is a cellular iron storage protein that can also be secreted by the exosome pathway, and serum ferritin levels classically reflect body iron stores. Iron metabolism-associated proteins such as ferritin are intricately regulated by cellular iron levels via the iron responsive element-iron regulatory protein (IRE-IRP) system. Herein, we present a novel mechanism demonstrating that the expression of the EV-associated protein CD63 is under the regulation of the IRE-IRP system. We discovered a canonical IRE in the 5' untranslated region of CD63 messenger RNA that is responsible for regulating its expression in response to increased iron. Cellular iron loading caused a marked increase in CD63 expression and the secretion of CD63+ EVs from cells, which were shown to contain ferritin-H and ferritin-L. Our results demonstrate that under iron loading, intracellular ferritin is transferred via nuclear receptor coactivator 4 (NCOA4) to CD63+ EVs that are then secreted. Such iron-regulated secretion of the major iron storage protein ferritin via CD63+ EVs, is significant for understanding the local cell-to-cell exchange of ferritin and iron.
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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.