Cited by 452Iron Metabolism and DisordersNeurological diseases and metabolismTrace Elements in Health

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Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway

Cohen, Lyora A., Gutierrez, Lucia, Weiss, Avital, Leichtmann-Bardoogo, Yael, Zhang, De-liang, Crooks, Daniel R., Sougrat, Rachid, Morgenstern, Avigail, Galy, Bruno, Hentze, Matthias W., Lazaro, Francisco J., Rouault, Tracey A., Meyron-Holtz, Esther G.·2010·Blood

DOI 10.1182/blood-2009-11-253815

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Abstract

The serum ferritin concentration is a clinical parameter measured widely for the differential diagnosis of anemia. Its levels increase with elevations of tissue iron stores and with inflammation, but studies on cellular sources of serum ferritin as well as its subunit composition, degree of iron loading and glycosylation have given rise to conflicting results. To gain further understanding of serum ferritin, we have used traditional and modern methodologies to characterize mouse serum ferritin. We find that both splenic macrophages and proximal tubule cells of the kidney are possible cellular sources for serum ferritin and that serum ferritin is secreted by cells rather than being the product of a cytosolic leak from damaged cells. Mouse serum ferritin is composed mostly of L-subunits, whereas it contains few H-subunits and iron content is low. L-subunits of serum ferritin are frequently truncated at the C-terminus, giving rise to a characteristic 17-kD band that has been previously observed in lysosomal ferritin. Taken together with the fact that mouse serum ferritin is not detectably glycosylated, we propose that mouse serum ferritin is secreted through the nonclassical lysosomal secretory pathway.

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“However, iron levels in secreted ferritin are low (12) and therefore unlikely to largely contribute to urinary iron excretion.”
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“Ferritin, the primary intracellular iron-storage protein, is composed of heavy (Fth) and light (Ftl) chains and capable of binding more than 4500 atoms of iron which can be mobilized for metabolic purposes through lysosomal degradation (Cohen et al., 2010; De Domenico et al., 2006).”
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“Macrophages, which were identified as the primary source of extracellular ferritin [153], secrete ferritin through a NCOA4-independent lysosomal pathway involving secretory autophagosomes [154] as well as via the multivesicular body–exosome pathway [155]. well as via the multivesicular body–exosome…”

Authors: Cohen, L. A., Gutierrez, L., Weiss, A., Leichtmann-Bardoogo, Y., Zhang, D.-L., Crooks, D. R., Sougrat, R., Morgenstern, A., Galy, B., Hentze, M. W., Lazaro, F. J., Rouault, T. A., & Meyron-Holtz, E. G.
Affiliations: Technion – Israel Institute of Technology (IL)
Departamento de Ciencia y Tecnología de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza, Spain;
Laboratory for Molecular Nutrition, Faculty of Biotechnology and Food Engineering, Technion, Technion City, Haifa, Israel;
Molecular Medicine Program and
National Institutes of Health (US)
European Molecular Biology Laboratory (DE)
ORCID: Zhang, De-liang
Crooks, Daniel R.
Sougrat, Rachid
Galy, Bruno
Hentze, Matthias W.
Rouault, Tracey A.
Venue: Blood
Publisher: American Society of Hematology
Published: 2010-09-02
Volume: 116
Issue: 9
Pages: 1574-1584
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2009-11-253815
OpenAlex: W2153170511
Cited by: 452
References: 53
Citations by year: 2026: 8 · 2025: 34 · 2024: 33 · 2023: 30 · 2022: 43 · 2021: 45 · 2020: 35 · 2019: 34 · 2018: 31 · 2017: 24 · 2016: 23 · 2015: 33 · 2014: 18 · 2013: 24 · 2012: 17
FWCI: 11.41
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: serum ferritin, macrophages, lysosomal secretion, L subunit, H subunit, C-terminal truncation, glycosylation, proximal tubular epithelial cells, splenic macrophages, iron stores, mice
MeSH terms: Amino Acid Sequence, Animals, Enzyme-Linked Immunosorbent Assay, Ferritins, Glycosylation, Iron, Lysosomes, Macrophages, Male, Mice, Inbred C57BL, Molecular Sequence Data, Sequence Homology, Amino Acid, Iron Overload, Protein Subunits, Mice, Secretory Pathway

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Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway

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