Ubiquinone

evidence_span

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experimental_model

Reconstructed-protein biochemistry, crystallography and mutagenesis

exposure

ATP-dependent pocket gating; excess final CoQ product

limitations

2026 reconstructed system using short-chain intermediates; do not assign all kinetics directly to intact human mitochondria.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Ancestral tetrapod COQ8A/COQ8B and COQ metabolon

plain_language

The finished product can feed back on its own synthesis machinery.

primary_references

[coq10-p42525751] COQ8 chaperones coenzyme Q lipid intermediates through ATP-driven structural gating. (2026). https://pubmed.ncbi.nlm.nih.gov/42525751/ DOI: 10.1126/sciadv.aeg1124

tissue_or_cell_type

Lipid-intermediate delivery

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 372–383

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstructed-protein biochemistry, crystallography and mutagenesis · source_derived_draft · unverified_draft

### coq10-coq-feedback Excess CoQ suppressed intermediate binding and the promoting effect of COQ8 in the reconstructed system. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The finished product can feed back on its own synthesis machinery. organism: Ancestral tetrapod COQ8A/COQ8B and COQ metabolon tissue_or_cell_type: Lipid-intermediate delivery experimental_model: Reconstructed-protein biochemistry, crystallography and mutagenesis limitations: 2026 reconstructed system using short-chain intermediates; do not assign all kinetics directly to intact human mitochondria. exposure: ATP-dependent pocket gating; excess final CoQ product evidence_span: {"source_cache": "artifacts/coq10-research/42525751.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b7a49b25f09323a11c782afbdbff069e95429ed28e0ce2da5519abcbaa76c632", "start_char": 0, "end_char": 1058, "text_sha256": "b7a49b25f09323a11c782afbdbff069e95429ed28e0ce2da5519abcbaa76c632"} [coq10-p42525751] COQ8 chaperones coenzyme Q lipid intermediates through ATP-driven structural gating. (2026). https://pubmed.ncbi.nlm.nih.gov/42525751/ DOI: 10.1126/sciadv.aeg1124

evidence_span

{"source_cache": "artifacts/coq10-research/17332895.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a500ba6d7c7b5f32817074367d71993504fbd9c5a10cb76038faf718fb79b87", "start_char": 0, "end_char": 1416, "text_sha256": "0a500ba6d7c7b5f32817074367d71993504fbd9c5a10cb76038faf718fb79b87"}

experimental_model

Pedigrees, respiratory assays and yeast complementation

exposure

PDSS1 D308E or COQ2 frameshift variants

limitations

Distinct families and mutations; quinone rescue in an assay is not equivalent to proven oral treatment of every organ.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Human families and yeast validation

plain_language

An intact respiratory enzyme can still fail when its mobile electron carrier is missing.

primary_references

[coq10-p17332895] Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. (2007). https://pubmed.ncbi.nlm.nih.gov/17332895/ DOI: 10.1172/jci29089

tissue_or_cell_type

CoQ-dependent respiratory function

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 216–227

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pedigrees, respiratory assays and yeast complementation · source_derived_draft · unverified_draft

### coq10-quinone-rescue-assay Adding quinone restored CoQ-dependent respiratory activities in the tested deficient preparations. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intact respiratory enzyme can still fail when its mobile electron carrier is missing. organism: Human families and yeast validation tissue_or_cell_type: CoQ-dependent respiratory function experimental_model: Pedigrees, respiratory assays and yeast complementation limitations: Distinct families and mutations; quinone rescue in an assay is not equivalent to proven oral treatment of every organ. exposure: PDSS1 D308E or COQ2 frameshift variants evidence_span: {"source_cache": "artifacts/coq10-research/17332895.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a500ba6d7c7b5f32817074367d71993504fbd9c5a10cb76038faf718fb79b87", "start_char": 0, "end_char": 1416, "text_sha256": "0a500ba6d7c7b5f32817074367d71993504fbd9c5a10cb76038faf718fb79b87"} [coq10-p17332895] Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. (2007). https://pubmed.ncbi.nlm.nih.gov/17332895/ DOI: 10.1172/jci29089

evidence_span

{"source_cache": "artifacts/coq10-research/25339443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30231d534c146d800ac3035cced0e6ce0ba810d871b40967a5483a19ee90f1a5", "start_char": 0, "end_char": 1471, "text_sha256": "30231d534c146d800ac3035cced0e6ce0ba810d871b40967a5483a19ee90f1a5"}

experimental_model

Mouse disease model, protein structure and lipid-binding assays

exposure

COQ9 R239X disease model and purified COQ9

limitations

Protein loss is not dietary CoQ shortage; lipid-presentation details include mechanistic inference.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Mouse Coq9 mutant and human COQ9 structure

plain_language

CoQ synthesis involves lipid handling as well as chemical reactions.

primary_references

[coq10-p25339443] Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis. (2014). https://pubmed.ncbi.nlm.nih.gov/25339443/ DOI: 10.1073/pnas.1413128111

tissue_or_cell_type

COQ9-COQ7 interaction

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 307–318

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse disease model, protein structure and lipid-binding assays · source_derived_draft · unverified_draft

### coq10-coq9-binding Purified COQ9 associated with lipids including CoQ and used a conserved surface to interact with COQ7. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoQ synthesis involves lipid handling as well as chemical reactions. organism: Mouse Coq9 mutant and human COQ9 structure tissue_or_cell_type: COQ9-COQ7 interaction experimental_model: Mouse disease model, protein structure and lipid-binding assays limitations: Protein loss is not dietary CoQ shortage; lipid-presentation details include mechanistic inference. exposure: COQ9 R239X disease model and purified COQ9 evidence_span: {"source_cache": "artifacts/coq10-research/25339443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30231d534c146d800ac3035cced0e6ce0ba810d871b40967a5483a19ee90f1a5", "start_char": 0, "end_char": 1471, "text_sha256": "30231d534c146d800ac3035cced0e6ce0ba810d871b40967a5483a19ee90f1a5"} [coq10-p25339443] Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis. (2014). https://pubmed.ncbi.nlm.nih.gov/25339443/ DOI: 10.1073/pnas.1413128111

evidence_span

{"source_cache": "artifacts/coq10-research/33981038.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b", "start_char": 0, "end_char": 1716, "text_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b"}

experimental_model

Genetic and pharmacological cancer-cell studies

exposure

DHODH loss or brequinar, with GPX4 inhibition

limitations

Pharmacological attribution and relative DHODH contribution were directly challenged in 2023; preserve the dispute rather than generalizing to dietary CoQ effects.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Human cancer-cell and tumor models

plain_language

A pyrimidine-synthesis enzyme can also contribute reduced CoQ in the studied system.

primary_references

[coq10-p33981038] DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. (2021). https://pubmed.ncbi.nlm.nih.gov/33981038/ DOI: 10.1038/s41586-021-03539-7

tissue_or_cell_type

Mitochondrial ferroptosis defense

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 814–825

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and pharmacological cancer-cell studies · source_derived_draft · unverified_draft

### coq10-dhodh-quinol The study reported DHODH-dependent ubiquinol generation as a mitochondrial ferroptosis-defense pathway. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A pyrimidine-synthesis enzyme can also contribute reduced CoQ in the studied system. organism: Human cancer-cell and tumor models tissue_or_cell_type: Mitochondrial ferroptosis defense experimental_model: Genetic and pharmacological cancer-cell studies limitations: Pharmacological attribution and relative DHODH contribution were directly challenged in 2023; preserve the dispute rather than generalizing to dietary CoQ effects. exposure: DHODH loss or brequinar, with GPX4 inhibition evidence_span: {"source_cache": "artifacts/coq10-research/33981038.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b", "start_char": 0, "end_char": 1716, "text_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b"} [coq10-p33981038] DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. (2021). https://pubmed.ncbi.nlm.nih.gov/33981038/ DOI: 10.1038/s41586-021-03539-7

evidence_span

{"source_cache": "artifacts/coq10-research/35749365.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d8219ff3cd63697715c88c25a9e558315bcd95c25bbc38f76987544bfee7581", "start_char": 0, "end_char": 1142, "text_sha256": "8d8219ff3cd63697715c88c25a9e558315bcd95c25bbc38f76987544bfee7581"}

experimental_model

Metabolomics, genetic deletion and tumor experiments

exposure

G3P supply and GPD2/GPX4 loss

limitations

Preclinical mechanism; no evidence that glycerol or CoQ supplements treat cancer.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Cancer-cell and tumor models

plain_language

Another metabolic input feeds the same reduced CoQ pool.

primary_references

[coq10-p35749365] A ferroptosis defense mechanism mediated by glycerol-3-phosphate dehydrogenase 2 in mitochondria. (2022). https://pubmed.ncbi.nlm.nih.gov/35749365/ DOI: 10.1073/pnas.2121987119

tissue_or_cell_type

Mitochondrial glycerol-phosphate oxidation

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 853–864

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolomics, genetic deletion and tumor experiments · source_derived_draft · unverified_draft

### coq10-gpd2-quinol GPD2 coupled glycerol-3-phosphate oxidation to ubiquinol formation. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another metabolic input feeds the same reduced CoQ pool. organism: Cancer-cell and tumor models tissue_or_cell_type: Mitochondrial glycerol-phosphate oxidation experimental_model: Metabolomics, genetic deletion and tumor experiments limitations: Preclinical mechanism; no evidence that glycerol or CoQ supplements treat cancer. exposure: G3P supply and GPD2/GPX4 loss evidence_span: {"source_cache": "artifacts/coq10-research/35749365.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d8219ff3cd63697715c88c25a9e558315bcd95c25bbc38f76987544bfee7581", "start_char": 0, "end_char": 1142, "text_sha256": "8d8219ff3cd63697715c88c25a9e558315bcd95c25bbc38f76987544bfee7581"} [coq10-p35749365] A ferroptosis defense mechanism mediated by glycerol-3-phosphate dehydrogenase 2 in mitochondria. (2022). https://pubmed.ncbi.nlm.nih.gov/35749365/ DOI: 10.1073/pnas.2121987119

evidence_span

{"source_cache": "artifacts/coq10-research/27856618.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485", "start_char": 0, "end_char": 1261, "text_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485"}

experimental_model

Patient fibroblasts, biosynthesis inhibition and mouse genetics

exposure

Genetic or pharmacological CoQ depletion and in-vitro repletion

limitations

Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Human fibroblasts/HeLa cells and Pdss2 mutant mice

plain_language

CoQ connects energy metabolism to sulfur disposal.

primary_references

[coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356

tissue_or_cell_type

Sulfide oxidation and tissue CoQ

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 528–539

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblasts, biosynthesis inhibition and mouse genetics · source_derived_draft · unverified_draft

### coq10-sqor-electron-acceptor CoQ serves as electron acceptor for SQOR at the start of mitochondrial sulfide oxidation. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoQ connects energy metabolism to sulfur disposal. organism: Human fibroblasts/HeLa cells and Pdss2 mutant mice tissue_or_cell_type: Sulfide oxidation and tissue CoQ experimental_model: Patient fibroblasts, biosynthesis inhibition and mouse genetics limitations: Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds. exposure: Genetic or pharmacological CoQ depletion and in-vitro repletion evidence_span: {"source_cache": "artifacts/coq10-research/27856618.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485", "start_char": 0, "end_char": 1261, "text_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485"} [coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356

evidence_span

{"source_cache": "artifacts/coq10-research/36658222.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce", "start_char": 0, "end_char": 1410, "text_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce"}

experimental_model

Protein processing, localization, transport and cell-growth experiments

exposure

PARL processing and compartment-specific STARD7 expression

limitations

Purified-protein binding with a CoQ variant; not demonstrated dietary choline competition with CoQ10 absorption.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Mammalian cell models

plain_language

Choline-containing membrane lipid and a CoQ analogue shared access to a transport protein.

primary_references

[coq10-p36658222] Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7. (2023). https://pubmed.ncbi.nlm.nih.gov/36658222/ DOI: 10.1038/s41556-022-01071-y

tissue_or_cell_type

Mitochondria and plasma membrane

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 502–513

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein processing, localization, transport and cell-growth experiments · source_derived_draft · unverified_draft

### coq10-stard7-pc A CoQ variant competed with phosphatidylcholine for binding to purified STARD7. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline-containing membrane lipid and a CoQ analogue shared access to a transport protein. organism: Mammalian cell models tissue_or_cell_type: Mitochondria and plasma membrane experimental_model: Protein processing, localization, transport and cell-growth experiments limitations: Purified-protein binding with a CoQ variant; not demonstrated dietary choline competition with CoQ10 absorption. exposure: PARL processing and compartment-specific STARD7 expression evidence_span: {"source_cache": "artifacts/coq10-research/36658222.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce", "start_char": 0, "end_char": 1410, "text_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce"} [coq10-p36658222] Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7. (2023). https://pubmed.ncbi.nlm.nih.gov/36658222/ DOI: 10.1038/s41556-022-01071-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 2, "char_start": 0, "char_end": 1789, "evidence_access": "full-text"}]

experimental_model

Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR.

exposure

Site-directed mutants compared with wild type.

limitations

Bacterial variant experiment; mechanism cannot be assigned quantitatively to human disease variants.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rhodobacter sphaeroides; human ETF/MCAD reagents

plain_language

Changing the flavin environment selectively impaired the quinone-reducing step.

primary_references

[swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

tissue_or_cell_type

Purified recombinant proteins

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 781–792

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. · source_derived_draft · unverified_draft

### b2-met-etf-qo-fad-quinone-function Rhodobacter ETF-QO N338T and N338A lowered FAD redox potentials and quinone-reductase activity while minimally affecting ETF semiquinone disproportionation. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the flavin environment selectively impaired the quinone-reducing step. organism: Rhodobacter sphaeroides; human ETF/MCAD reagents tissue_or_cell_type: Purified recombinant proteins experimental_model: Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. limitations: Bacterial variant experiment; mechanism cannot be assigned quantitatively to human disease variants. exposure: Site-directed mutants compared with wild type. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 2, "char_start": 0, "char_end": 1789, "evidence_access": "full-text"}] [swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

evidence_span

{"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"}

experimental_model

Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays

exposure

Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange

limitations

Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease.

nutrient_topic

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

organism

Human and mouse cells; additional rat vascular experiments in the paper

plain_language

The effect depended on how the respiratory machinery was organized.

primary_references

[sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

tissue_or_cell_type

Mitochondrial matrix and inner membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 798–809

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays · source_derived_draft · unverified_draft

### sodium-quinone-mobility The sodium-linked membrane change reduced free ubiquinone mobility between complexes II and III, while transport within supercomplexes was spared. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The effect depended on how the respiratory machinery was organized. organism: Human and mouse cells; additional rat vascular experiments in the paper tissue_or_cell_type: Mitochondrial matrix and inner membrane experimental_model: Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays limitations: Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease. exposure: Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange evidence_span: {"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"} [sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

evidence_span

{"source_cache": "artifacts/coq10-research/38243131.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "de9afaeca8a144d79c9f0d0d3b3faafaa4560af2292b8624d1a04ed45ee5d136", "start_char": 0, "end_char": 1039, "text_sha256": "de9afaeca8a144d79c9f0d0d3b3faafaa4560af2292b8624d1a04ed45ee5d136"}

experimental_model

Muscle-specific knockout and protein-complex analyses

exposure

Etfdh deletion and metabolon characterization

limitations

Skeletal-muscle context; does not establish identical complex organization in every human tissue.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Mouse skeletal muscle and biochemical systems

plain_language

Fat oxidation and CoQ synthesis connect to the complex that reoxidizes reduced CoQ.

primary_references

[coq10-p38243131] An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis. (2024). https://pubmed.ncbi.nlm.nih.gov/38243131/ DOI: 10.1038/s42255-023-00956-y

tissue_or_cell_type

ETFDH-complex III-COQ2 assembly

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 411–422

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Muscle-specific knockout and protein-complex analyses · source_derived_draft · unverified_draft

### coq10-etfdh-metabolon The study identified an ETFDH-complex III-COQ2 assembly directing lipid-derived electrons to the respiratory chain in skeletal muscle. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Fat oxidation and CoQ synthesis connect to the complex that reoxidizes reduced CoQ. organism: Mouse skeletal muscle and biochemical systems tissue_or_cell_type: ETFDH-complex III-COQ2 assembly experimental_model: Muscle-specific knockout and protein-complex analyses limitations: Skeletal-muscle context; does not establish identical complex organization in every human tissue. exposure: Etfdh deletion and metabolon characterization evidence_span: {"source_cache": "artifacts/coq10-research/38243131.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "de9afaeca8a144d79c9f0d0d3b3faafaa4560af2292b8624d1a04ed45ee5d136", "start_char": 0, "end_char": 1039, "text_sha256": "de9afaeca8a144d79c9f0d0d3b3faafaa4560af2292b8624d1a04ed45ee5d136"} [coq10-p38243131] An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis. (2024). https://pubmed.ncbi.nlm.nih.gov/38243131/ DOI: 10.1038/s42255-023-00956-y

cross_nutrient

Direct mechanistic integration of an iron-containing center with B2-derived FAD.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}]

experimental_model

Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rhodobacter sphaeroides; human ETF/MCAD reagents

plain_language

ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay.

primary_references

[swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

tissue_or_cell_type

Purified proteins

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 794–806

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. · source_derived_draft · unverified_draft

### b2-met-etf-qo-iron-sulfur-entry Selective effects of ETF-QO FAD-site mutations supported electron entry from ETF through the [4Fe-4S] center, followed by flavin-mediated transfer to ubiquinone. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay. organism: Rhodobacter sphaeroides; human ETF/MCAD reagents tissue_or_cell_type: Purified proteins experimental_model: Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. limitations: Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: Direct mechanistic integration of an iron-containing center with B2-derived FAD. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}] [swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

cross_nutrient

B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}]

experimental_model

Purified porcine ETF-QO crystal structures with and without bound ubiquinone.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Static structure; the exact electron-entry sequence required additional functional experiments.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Sus scrofa

plain_language

ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF.

primary_references

[zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103

tissue_or_cell_type

Purified porcine mitochondrial ETF-QO

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–779

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified porcine ETF-QO crystal structures with and without bound ubiquinone. · source_derived_draft · unverified_draft

### b2-met-porcine-etfdh-cofactors Porcine ETF-QO crystal structures resolved one FAD and one [4Fe-4S] cluster per protein, together with a separate ubiquinone-binding region. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF. organism: Sus scrofa tissue_or_cell_type: Purified porcine mitochondrial ETF-QO experimental_model: Purified porcine ETF-QO crystal structures with and without bound ubiquinone. limitations: Static structure; the exact electron-entry sequence required additional functional experiments. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}] [zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103

evidence_access

Primary indexed abstract and figure descriptions.

experimental_model

Purified human sulfide:quinone oxidoreductase; transient kinetics and flavin spectroscopy.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Enzyme-bound FAD is not extracellular FMN. This study did not test dietary B2 deficiency or combined B2 and ergothioneine treatment.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Sulfur disposal has a flavin-dependent electron relay.

primary_references

Mishanina et al. Transient Kinetic Analysis of Hydrogen Sulfide Oxidation Catalyzed by Human Sulfide Quinone Oxidoreductase. DOI 10.1074/jbc.M115.682369; PMID 26318450; https://pubmed.ncbi.nlm.nih.gov/26318450/

source_locator

Abstract and Figure 1

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 129–129

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human sulfide:quinone oxidoreductase; transient kinetics and flavin spectroscopy. · source_derived_draft · unverified_draft

Bound FAD cycles between reduction by sulfide and oxidation by ubiquinone during human SQOR catalysis.

evidence_access

Primary indexed abstract. Physiological acceptor assignment is a kinetic interpretation, not a direct measurement of flux in a patient.

experimental_model

Purified human SQOR in nanodiscs; steady-state and rapid-kinetic assays.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Predominant acceptor is a kinetic interpretation; alternative acceptors can work in other assay conditions. Ergothioneine and nutrient depletion were not tested.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Glutathione also participates in disposal of sulfide-derived sulfur.

primary_references

Landry et al. H2S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase. DOI 10.1074/jbc.M117.788547; PMID 28512131; https://pubmed.ncbi.nlm.nih.gov/28512131/

source_locator

Abstract

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 137–137

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human SQOR in nanodiscs; steady-state and rapid-kinetic assays. · source_derived_draft · unverified_draft

Nanodisc-embedded human SQOR transferred sulfane sulfur to glutathione; kinetics supported GSH as the predominant physiological acceptor.