Component

Ferritin heavy chain

Human ferritin heavy-chain subunit with ferroxidase function, used in overexpression experiments.

4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Ferritin-heavy-chain overexpression in H1299 cells lowered labile iron and increased clonogenic survival after pharmacological ascorbate, supporting a protective role of intracellular iron sequestration in this setting.

    Ferritin heavy chain → Cancer-cell clonogenic survival source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Figure 6I–L
    experimental_model
    H1299 adenoviral ferritin-heavy-chain versus empty-vector cultures; calcein/BIP and clonogenic assays
    exposure
    20-MOI ferritin-heavy-chain expression 36 h before experiment; 5 pmol/cell (approximately 2–3 mM) ascorbate for 1 h.
    limitations
    Engineered overexpression is not dietary iron deficiency or ordinary ferritin concentration; serum ferritin does not measure this intracellular intervention.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Homo sapiens
    plain_language
    Locking more iron into ferritin protected these lung cancer cells from the exposure.
    primary_references
    [c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018
    tissue_or_cell_type
    NSCLC cells

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1369–1381

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · H1299 adenoviral ferritin-heavy-chain versus empty-vector cultures; calcein/BIP and clonogenic assays · source_derived_draft · unverified_draft

    ### c-reg-ferritin-heavy-protects Ferritin-heavy-chain overexpression in H1299 cells lowered labile iron and increased clonogenic survival after pharmacological ascorbate, supporting a protective role of intracellular iron sequestration in this setting. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Locking more iron into ferritin protected these lung cancer cells from the exposure. organism: Homo sapiens tissue_or_cell_type: NSCLC cells experimental_model: H1299 adenoviral ferritin-heavy-chain versus empty-vector cultures; calcein/BIP and clonogenic assays limitations: Engineered overexpression is not dietary iron deficiency or ordinary ferritin concentration; serum ferritin does not measure this intracellular intervention. exposure: 20-MOI ferritin-heavy-chain expression 36 h before experiment; 5 pmol/cell (approximately 2–3 mM) ascorbate for 1 h. cross_nutrient: true evidence_location: Figure 6I–L [c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018
    Complete structured claim and evidence

  2. Human H-chain ferritin catalyzed Fe(II) oxidation; mutation of its proposed ferroxidase ligands Glu62 and His65 abolished most activity.

    Ferritin heavy chain → Ferrous iron source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"}
    experimental_model
    Ferroxidase kinetics and site-directed mutants
    exposure
    Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition
    limitations
    In-vitro metal concentrations and H/L composition determine kinetics; this does not establish a dietary zinc effect on human iron stores.
    nutrient_topic
    Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
    organism
    Human recombinant ferritin and human liver apoferritin
    plain_language
    Ferritin does chemical work to package iron, not just physical storage.
    primary_references
    [iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
    tissue_or_cell_type
    Purified ferritin subunits/assemblies

    Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 615–626

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ferroxidase kinetics and site-directed mutants · source_derived_draft · unverified_draft

    ### iron-ferritin-h-oxidation Human H-chain ferritin catalyzed Fe(II) oxidation; mutation of its proposed ferroxidase ligands Glu62 and His65 abolished most activity. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ferritin does chemical work to package iron, not just physical storage. organism: Human recombinant ferritin and human liver apoferritin tissue_or_cell_type: Purified ferritin subunits/assemblies experimental_model: Ferroxidase kinetics and site-directed mutants limitations: In-vitro metal concentrations and H/L composition determine kinetics; this does not establish a dietary zinc effect on human iron stores. exposure: Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition evidence_span: {"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"} [iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Recombinant human L-chain ferritin lacked ferroxidase activity, although H/L assembly composition altered whole-ferritin oxidation kinetics.

    Human ferritin light chain / FTL → Ferritin ferroxidase activity source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"}
    experimental_model
    Ferroxidase kinetics and site-directed mutants
    exposure
    Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition
    limitations
    Purified recombinant subunits; H/L assembly kinetics do not establish a dietary zinc effect on human iron stores.
    nutrient_topic
    Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
    organism
    Human recombinant ferritin and human liver apoferritin
    plain_language
    The heavy and light chains play different roles in the storage cage.
    primary_references
    [iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
    tissue_or_cell_type
    Purified ferritin subunits/assemblies

    Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 628–639

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ferroxidase kinetics and site-directed mutants · source_derived_draft · unverified_draft

    ### iron-ferritin-l-distinction Recombinant human L-chain ferritin lacked ferroxidase activity, although H/L assembly composition altered whole-ferritin oxidation kinetics. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The heavy and light chains play different roles in the storage cage. organism: Human recombinant ferritin and human liver apoferritin tissue_or_cell_type: Purified ferritin subunits/assemblies experimental_model: Ferroxidase kinetics and site-directed mutants limitations: Purified recombinant subunits; H/L assembly kinetics do not establish a dietary zinc effect on human iron stores. exposure: Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition evidence_span: {"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"} [iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
    Complete structured claim and evidence

  2. NCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes.

    Human nuclear receptor coactivator 4 / NCOA4 → Lysosomal delivery and degradation of ferritin source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/iron-research/24695223.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a", "start_char": 0, "end_char": 1514, "text_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a"}
    experimental_model
    Quantitative proteomics and selective-autophagy experiments
    exposure
    NCOA4 association and loss experiments
    limitations
    Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration.
    nutrient_topic
    Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
    organism
    Human cultured cells
    plain_language
    A selective cargo receptor sends stored iron for release when cells need it.
    primary_references
    [iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148
    tissue_or_cell_type
    Autophagosomes and lysosomes

    Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 641–652

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative proteomics and selective-autophagy experiments · source_derived_draft · unverified_draft

    ### iron-ncoa4-ferritin NCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A selective cargo receptor sends stored iron for release when cells need it. organism: Human cultured cells tissue_or_cell_type: Autophagosomes and lysosomes experimental_model: Quantitative proteomics and selective-autophagy experiments limitations: Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration. exposure: NCOA4 association and loss experiments evidence_span: {"source_cache": "artifacts/iron-research/24695223.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a", "start_char": 0, "end_char": 1514, "text_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a"} [iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards