ArticleBlood2018
Ferritin is secreted via 2 distinct nonclassical vesicular pathways.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 218 citations in OpenAlex.
- The role of iron in normal and impaired testicular function.Andrology · 2026Review
- Altered iron metabolism and iron therapy in restless legs syndrome.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Dysregulated ferritin and iron homeostasis in autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2026Article
- Hyperferritinemia: Pathophysiology, Etiologies, and Diagnostic Approach.European journal of haematology · 2026Review
- Review
- Iron Salts, but Not Iron Oxide Nanoparticles, Drive High-Yield Production of Iron-Engineered Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- Lipid-manager autophagy proteins ATG2 and ATG9 regulate extracellular vesicle secretion via amphisome biogenesis and cell lipidome modulation.Nature communications · 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
- Comparative proteomics reveals protein signatures shared between and unique to bona fide plant EVs and other plant-derived vesicles.Plant physiology · 2026Article
- Mechanisms of the RGS12-GPX4-ACSL4 signaling axis in regulating ferroptosis during myocardial ischemia-reperfusion injury.Journal of anesthesia and translational medicine · 2026Review
- Targeted deletion of macrophage ferritin heavy chain protects from macrophage ferroptosis in acute respiratory distress syndrome.Research square · 2026Article
- Iron-related intercellular communication in the liver: Main players and mechanisms.European journal of clinical investigation · 2026Review
- The Time Course of Serum Iron and Serum Ferritin Concentrations Post-COVID-19 and Influenza Vaccinations.Case reports in infectious diseases · 2026Article
- Mechanism and therapeutic prospects of ferroptosis regulation through m6A in cancer.Frontiers in cell and developmental biology · 2026Review
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Extracellular iron and the lung microbiome in smoking and COPD.ERJ open research · 2025Article
- Comparative Proteomic Analysis of Extracellular Vesicles from Donkey Colostrum and Mature Milk.Metabolites · 2025Article
- Assessment of Hemophagocytic Lympho-Histiocytosis (HLH) in the Setting of Adult Acute Liver Failure.Journal of viral hepatitis · 2025Article
- Iron metabolism and ferroptosis in human health and disease.BMC biology · 2025Review
73 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
Abstract
Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum-Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body-exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis.
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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.