ArticlePloS one2012
Subcellular localization of iron and heme metabolism related proteins at early stages of erythrophagocytosis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Association Analysis ofAnimals : an open access journal from MDPI · 2025Article
- Research progress on the cross-regulation between ferroptosis and immunogenic cell death in tumor micro-environment.Frontiers in oncology · 2025Review
- Molecular and Immunometabolic Landscape of Erythrophagocytosis-induced Ferroptosis.Cardiovascular & hematological disorders drug targets · 2025Review
- Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats.Journal of cachexia, sarcopenia and muscle · 2024Article
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- A mouse model characterizes the roles of ZIP8 in systemic iron recycling and lung inflammation and infection.Blood advances · 2023Article
- Article
- Iron homeostasis and post-hemorrhagic hydrocephalus: a review.Frontiers in neurology · 2023Review
- Defining solute carrier transporter signatures of murine immune cell subsets.Frontiers in immunology · 2023Article
- Crosstalk between Heme Oxygenase-1 and Iron Metabolism in Macrophages: Implications for the Modulation of Inflammation and Immunity.Antioxidants (Basel, Switzerland) · 2022Review
- The Multiple Facets of Iron Recycling.Genes · 2021Review
- Molecular Mechanism of Nramp-Family Transition Metal Transport.Journal of molecular biology · 2021Review
- Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis.International journal of molecular sciences · 2021Review
- Heme in Cardiovascular Diseases: A Ubiquitous Dangerous Molecule Worthy of Vigilance.Frontiers in cell and developmental biology · 2021Review
- Iron and Heme Metabolism at the Leishmania-Host Interface.Trends in parasitology · 2020Review
- Article
- Label-free characterization of white blood cells using fluorescence lifetime imaging and flow-cytometry: molecular heterogeneity and erythrophagocytosis [Invited].Biomedical optics express · 2019Article
- Role of the kidneys in the redistribution of heme-derived iron during neonatal hemolysis in mice.Scientific reports · 2019Article
- Iron-Dependent Trafficking of 5-Lipoxygenase and Impact on Human Macrophage Activation.Frontiers in immunology · 2019Article
- Iron Regulation: Macrophages in Control.Pharmaceuticals (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSenescent red blood cells (RBC) are recognized, phagocytosed and cleared by tissue macrophages. During this erythrophagocytosis (EP), RBC are engulfed and processed in special compartments called erythrophagosomes. We previously described that following EP, heme is rapidly degraded through the catabolic activity of heme oxygenase (HO). Extracted heme iron is then either exported or stored by macrophages. However, the cellular localization of the early steps of heme processing and iron extraction during EP remains to be clearly defined. METHODOLOGY/PRINCIPAL
findingsWe took advantage of our previously described cellular model of EP, using bone marrow-derived macrophages (BMDM). The subcellular localization of both inducible and constitutive isoforms of HO (HO-1 and HO-2), of the divalent metal transporters (Nramp1, Nramp2/DMT1, Fpn), and of the recently identified heme transporter HRG-1, was followed by fluorescence and electron microscopy during the earliest steps of EP. We also looked at some ER [calnexin, glucose-6-phosphatase (G6Pase) activity] and lysosomes (Lamp1) markers during EP. In both quiescent and LPS-activated BMDM, Nramp1 and Lamp1 were shown to be strong markers of the erythrophagolysosomal membrane. HRG-1 was also recruited to the erythrophagosome. Furthermore, we observed calnexin labeling and G6Pase activity at the erythrophagosomal membrane, indicating the contribution of ER in this phagocytosis model. In contrast, Nramp2/DMT1, Fpn, HO-1 and HO-2 were not detected at the membrane of erythrophagosomes. CONCLUSIONS/SIGNIFICANCE: Our study highlights the subcellular localization of various heme- and iron-related proteins during early steps of EP, thereby suggesting a model for heme catabolism occurring outside the phagosome, with heme likely being transported into the cytosol through HRG1. The precise function of Nramp1 at the phagosomal membrane in this model remains to be determined.
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