ArticleBlood advances2022
Lysosomal iron recycling in mouse macrophages is dependent upon both LcytB and Steap3 reductases.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
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- Neuroprotective Nanoplatform Integrating Antioxidant MXene Nanozymes and Ferroptosis Inhibitors for Targeted Therapy of Cerebral Ischemia-Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adaptive resilience: agarikon mycelium modulates immune responses and provides oxidative stress buffering in human immune cells.Frontiers in immunology · 2026Article
- Iron as an immunometabolic signal in infection and inflammation.Frontiers in immunology · 2026Review
- Iron-related intercellular communication in the liver: Main players and mechanisms.European journal of clinical investigation · 2026Review
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- Toxicity of Magnetic Nanoparticles in Medicine: Contributing Factors and Modern Assessment Methods.International journal of molecular sciences · 2025Review
- Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy.Comprehensive Physiology · 2025Review
- Article
- Role of the human cytochrome b561 family in iron metabolism and tumors (Review).Oncology letters · 2025Review
- Ferroptosis: iron release mechanisms in the bioenergetic process.Cancer metastasis reviews · 2025Review
- Fluoride Induces Neurocytotoxicity by Disrupting Lysosomal Iron Metabolism and Membrane Permeability.Biological trace element research · 2025Article
- Cellular Iron Homeostasis.Advances in experimental medicine and biology · 2025Review
- Lysosome-Iron-Mitochondria Axis in Osteoclasts: Iron as a Central Player.Research (Washington, D.C.) · 2025Review
- Endo-Lysosomal Network Disorder Reprograms Energy Metabolism in SorL1-Null Rat Hippocampus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nrf2-mediated ferroptosis inhibition: a novel approach for managing inflammatory diseases.Inflammopharmacology · 2024Review
- Synthetic vectors for activating the driving axis of ferroptosis.Nature communications · 2024Article
- Bortezomib elevates intracellular free FeAnnals of hematology · 2024Article
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Iron that is stored in macrophages as ferritin can be made bioavailable by degrading ferritin in the lysosome and releasing iron back into the cytosol. Iron stored in ferritin is found as Fe3+ and must be reduced to Fe2+ before it can be exported from the lysosome. Here we report that the lysosomal reductase Cyb561a3 (LcytB) and the endosomal reductase six-transmembrane epithelial antigen of prostate 3 (Steap3) act as lysosomal ferrireductases in the mouse macrophage cell line RAW264.7 converting Fe3+ to Fe2+ for iron recycling. We determined that when lysosomes were loaded with horse cationic ferritin, reductions or loss of LcytB or Steap3 using CRISPR/Cas9-mediated knockout technology resulted in decreased lysosomal iron export. Loss of both reductases was additive in decreasing lysosomal iron export. Decreased reductase activity resulted in increased transcripts for iron acquisition proteins DMT1 and transferrin receptor 1 (Tfrc1) suggesting that cells were iron limited. We show that transcript expression of LcytB and Steap3 is decreased in macrophages exposed to Escherichia coli pathogen UTI89, which supports a role for these reductases in regulating iron availability for pathogens. We further show that loss of LcytB and Steap3 in macrophages infected with UTI89 led to increased proliferation of intracellular UTI89 suggesting that the endolysosomal system is retaining Fe3+ that can be used for proliferation of intravesicular pathogens. Together, our findings reveal an important role for both LcytB and Steap3 in macrophage iron recycling and suggest that limiting iron recycling by decreasing expression of endolysosomal reductases is an innate immune response to protect against pathogen proliferation and sepsis.
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