Cellular labile iron pool

evidence_span

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experimental_model

Intracellular chelation with simultaneous EPR measurements

exposure

Hydroxypyridinone versus desferrioxamine chelation and washout

limitations

Pharmacological cell experiment; radical loss is not a direct clinical measure of nutritional iron deficiency.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Human leukemia K562 cells

plain_language

Iron locked away by a chelator was not equally available to maintain the DNA-synthesis enzyme.

primary_references

[iron-p8702762] The relationship of intracellular iron chelation to the inhibition and regeneration of human ribonucleotide reductase. (1996). https://pubmed.ncbi.nlm.nih.gov/8702762/ DOI: 10.1074/jbc.271.34.20291

tissue_or_cell_type

Intracellular iron pool and ribonucleotide reductase

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1200–1211

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intracellular chelation with simultaneous EPR measurements · source_derived_draft · unverified_draft

### iron-chelation-rr Intracellular iron chelation removed the ribonucleotide-reductase tyrosyl radical, with depletion and regeneration kinetics depending on the chelator. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron locked away by a chelator was not equally available to maintain the DNA-synthesis enzyme. organism: Human leukemia K562 cells tissue_or_cell_type: Intracellular iron pool and ribonucleotide reductase experimental_model: Intracellular chelation with simultaneous EPR measurements limitations: Pharmacological cell experiment; radical loss is not a direct clinical measure of nutritional iron deficiency. exposure: Hydroxypyridinone versus desferrioxamine chelation and washout evidence_span: {"source_cache": "artifacts/iron-research/8702762.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ceb70db961d5ae6f975c9edf1df28c495811a38189831240b8e3e61530b3a7f0", "start_char": 0, "end_char": 1525, "text_sha256": "ceb70db961d5ae6f975c9edf1df28c495811a38189831240b8e3e61530b3a7f0"} [iron-p8702762] The relationship of intracellular iron chelation to the inhibition and regeneration of human ribonucleotide reductase. (1996). https://pubmed.ncbi.nlm.nih.gov/8702762/ DOI: 10.1074/jbc.271.34.20291

evidence_span

{"source_cache": "artifacts/iron-research/22632970.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0", "start_char": 0, "end_char": 1089, "text_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0"}

experimental_model

Chemical and genetic characterization of nonapoptotic cell death

exposure

Erastin and ferrostatin-1 experiments

limitations

Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Cancer-cell systems and rat brain slices

plain_language

Usable iron is essential, but under particular conditions it also enables oxidative cell death.

primary_references

[iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. (2012). https://pubmed.ncbi.nlm.nih.gov/22632970/ DOI: 10.1016/j.cell.2012.03.042

tissue_or_cell_type

Cellular iron, cystine transport and oxidative injury

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1226–1237

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical and genetic characterization of nonapoptotic cell death · source_derived_draft · unverified_draft

### iron-iron-ferroptosis Erastin-induced ferroptosis depended on intracellular iron and was distinct from apoptosis, necrosis and autophagy in the study. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Usable iron is essential, but under particular conditions it also enables oxidative cell death. organism: Cancer-cell systems and rat brain slices tissue_or_cell_type: Cellular iron, cystine transport and oxidative injury experimental_model: Chemical and genetic characterization of nonapoptotic cell death limitations: Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure. exposure: Erastin and ferrostatin-1 experiments evidence_span: {"source_cache": "artifacts/iron-research/22632970.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0", "start_char": 0, "end_char": 1089, "text_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0"} [iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. (2012). https://pubmed.ncbi.nlm.nih.gov/22632970/ DOI: 10.1016/j.cell.2012.03.042

availability_state

machinery_impairment Imported condition classification; unverified.

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

The cell could have iron in a storage cage while still lacking usable iron.

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

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 654–665

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-loss NCOA4-deficient cells could not degrade ferritin normally and had decreased bioavailable intracellular iron. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell could have iron in a storage cage while still lacking usable iron. 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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/18511687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68", "start_char": 0, "end_char": 703, "text_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68"}

experimental_model

Yeast expression, in-vitro binding/loading and human-cell depletion

exposure

PCBP1 expression and depletion

limitations

Chaperone-mediated distribution is distinct from total cellular iron.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Human PCBP1 and ferritin in yeast and human cells

plain_language

Less iron in storage can coexist with more potentially reactive iron outside the store.

primary_references

[iron-p18511687] A cytosolic iron chaperone that delivers iron to ferritin. (2008). https://pubmed.ncbi.nlm.nih.gov/18511687/ DOI: 10.1126/science.1157643

tissue_or_cell_type

Cytosol

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 602–613

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast expression, in-vitro binding/loading and human-cell depletion · source_derived_draft · unverified_draft

### iron-pcbp-depletion PCBP1 depletion inhibited ferritin iron loading and increased cytosolic iron pools in human cells. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less iron in storage can coexist with more potentially reactive iron outside the store. organism: Human PCBP1 and ferritin in yeast and human cells tissue_or_cell_type: Cytosol experimental_model: Yeast expression, in-vitro binding/loading and human-cell depletion limitations: Chaperone-mediated distribution is distinct from total cellular iron. exposure: PCBP1 expression and depletion evidence_span: {"source_cache": "artifacts/iron-research/18511687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68", "start_char": 0, "end_char": 703, "text_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68"} [iron-p18511687] A cytosolic iron chaperone that delivers iron to ferritin. (2008). https://pubmed.ncbi.nlm.nih.gov/18511687/ DOI: 10.1126/science.1157643

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

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Figure 5C–E

experimental_model

SOD2-null versus parental A549; calcein/BIP labile-iron assay and clonogenic survival

exposure

10 pmol/cell (2 mM) ascorbate for 1 h; LIP measured with 500 nM calcein-AM and 100 µM 2,2′-bipyridyl dequenching.

limitations

SOD2 genotype is not dietary manganese deficiency; DHE oxidation alone is not chemically specific proof of superoxide. Study does not identify a universal cancer-selectivity mechanism.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Removing a mitochondrial antioxidant enzyme made these lung cancer cells more vulnerable to the high-dose 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

Lung adenocarcinoma cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1355–1367

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SOD2-null versus parental A549; calcein/BIP labile-iron assay and clonogenic survival · source_derived_draft · unverified_draft

### c-reg-sod2-loss-sensitizes SOD2 knockout A549 cells had higher basal labile iron and greater clonogenic killing by ascorbate than parental cells, linking antioxidant machinery impairment to sensitivity in this model. Condition category: machinery_impairment nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing a mitochondrial antioxidant enzyme made these lung cancer cells more vulnerable to the high-dose exposure. organism: Homo sapiens tissue_or_cell_type: Lung adenocarcinoma cells experimental_model: SOD2-null versus parental A549; calcein/BIP labile-iron assay and clonogenic survival limitations: SOD2 genotype is not dietary manganese deficiency; DHE oxidation alone is not chemically specific proof of superoxide. Study does not identify a universal cancer-selectivity mechanism. exposure: 10 pmol/cell (2 mM) ascorbate for 1 h; LIP measured with 500 nM calcein-AM and 100 µM 2,2′-bipyridyl dequenching. cross_nutrient: true evidence_location: Figure 5C–E [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