Mitochondrial respiratory complex I

evidence_span

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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

Low oxygen can change mitochondrial chemistry before sodium enters.

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 746–757

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-hypoxia-acid A hypoxia-associated conformational change in complex I drove matrix acidification in the proposed and experimentally supported pathway. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low oxygen can change mitochondrial chemistry before sodium enters. 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/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"}

experimental_model

Proteoliposome enzyme kinetics

exposure

Ubiquinones with one to ten isoprenoid units

limitations

Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10.

nutrient_topic

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

organism

Mammalian complex I preparation

plain_language

CoQ receives electrons from the first respiratory complex.

primary_references

[coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114

tissue_or_cell_type

Membrane quinone channel

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 385–396

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

### coq10-complex-i-q Complex I transferred electrons from NADH to ubiquinone-10 in reconstituted membranes. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoQ receives electrons from the first respiratory complex. organism: Mammalian complex I preparation tissue_or_cell_type: Membrane quinone channel experimental_model: Proteoliposome enzyme kinetics limitations: Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10. exposure: Ubiquinones with one to ten isoprenoid units evidence_span: {"source_cache": "artifacts/coq10-research/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"} [coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114

evidence_span

{"source_cache": "artifacts/coq10-research/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"}

experimental_model

Proteoliposome enzyme kinetics

exposure

Ubiquinones with one to ten isoprenoid units

limitations

Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10.

nutrient_topic

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

organism

Mammalian complex I preparation

plain_language

The ten-unit tail is part of the working molecule, not an inert label.

primary_references

[coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114

tissue_or_cell_type

Membrane quinone channel

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 398–409

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

### coq10-complex-i-tail Ubiquinone-10 had the highest binding affinity and fastest binding rate among the tested chain lengths; ubiquinol-10 release was not rate limiting. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The ten-unit tail is part of the working molecule, not an inert label. organism: Mammalian complex I preparation tissue_or_cell_type: Membrane quinone channel experimental_model: Proteoliposome enzyme kinetics limitations: Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10. exposure: Ubiquinones with one to ten isoprenoid units evidence_span: {"source_cache": "artifacts/coq10-research/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"} [coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}]

experimental_model

Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.

exposure

10 micromolar riboflavin, FAD or FMN in the reconstitution comparison.

limitations

Does not test intact-cell conversion of riboflavin into FMN.

nutrient_topic

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

organism

Bos taurus

plain_language

Free B2 and FAD could not substitute directly for FMN in this test tube.

primary_references

[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

tissue_or_cell_type

Heart submitochondrial particles

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 596–607

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft

### b2-met-complex-i-flavin-specificity Riboflavin and FAD failed to protect or reactivate alkaline-inactivated bovine complex I under conditions where FMN did. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free B2 and FAD could not substitute directly for FMN in this test tube. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: Does not test intact-cell conversion of riboflavin into FMN. exposure: 10 micromolar riboflavin, FAD or FMN in the reconstitution comparison. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}]

experimental_model

Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.

exposure

10 micromolar FMN after NADH/respiratory blockade at pH 10.

limitations

pH 10 treatment; not a test of dietary deficiency or oral supplementation.

nutrient_topic

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

organism

Bos taurus

plain_language

Putting the correct flavin back restored this experimentally inactivated respiratory enzyme.

primary_references

[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

tissue_or_cell_type

Heart submitochondrial particles

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 570–581

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft

### b2-met-complex-i-fmn-reconstitution FMN restored rotenone-sensitive NADH:quinone reductase activity after alkaline reductive inactivation of bovine membrane-bound complex I. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Putting the correct flavin back restored this experimentally inactivated respiratory enzyme. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: pH 10 treatment; not a test of dietary deficiency or oral supplementation. exposure: 10 micromolar FMN after NADH/respiratory blockade at pH 10. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}]

experimental_model

Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.

exposure

NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays.

limitations

Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH.

nutrient_topic

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

organism

Bos taurus

plain_language

An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin.

primary_references

[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

tissue_or_cell_type

Heart submitochondrial particles

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 583–594

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft

### b2-met-complex-i-reductive-fmn-loss NADH plus respiratory blockade at alkaline pH caused time-dependent activity loss consistent with reversible FMN dissociation from bovine membrane-bound complex I. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH. exposure: NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]

experimental_model

Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.

exposure

Riboflavin-free medium; matched control contained 1 micromolar riboflavin.

limitations

Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold.

nutrient_topic

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

organism

Homo sapiens; Mus musculus

plain_language

Removing B2 reduced parts needed to build the respiratory enzyme.

primary_references

[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

tissue_or_cell_type

143B cells and mouse adult fibroblasts

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 609–620

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft

### b2-met-depletion-complex-i Riboflavin-free culture reduced complex I abundance; human 143B proteomics identified particularly strong loss of its NADH-oxidizing N-module subunits. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing B2 reduced parts needed to build the respiratory enzyme. organism: Homo sapiens; Mus musculus tissue_or_cell_type: 143B cells and mouse adult fibroblasts experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold. exposure: Riboflavin-free medium; matched control contained 1 micromolar riboflavin. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

evidence_span

{"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"}

experimental_model

Cell respiration, isolated mitochondria and kinase perturbation

exposure

Berberine concentration-response; kinase deletion/inhibition

limitations

Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy.

nutrient_topic

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

organism

Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells

plain_language

Slowing one respiratory-chain step can trigger a cellular energy response.

primary_references

[berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552

tissue_or_cell_type

Respiratory complex I and AMPK

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 324–335

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell respiration, isolated mitochondria and kinase perturbation · source_derived_draft · unverified_draft

### berberine-complex-i Berberine inhibited respiration in L6 myotubes and muscle mitochondria through a complex-I-associated effect. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Slowing one respiratory-chain step can trigger a cellular energy response. organism: Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells tissue_or_cell_type: Respiratory complex I and AMPK experimental_model: Cell respiration, isolated mitochondria and kinase perturbation limitations: Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy. exposure: Berberine concentration-response; kinase deletion/inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"} [berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552

cross_nutrient

true

evidence_location

Figure 6D

experimental_model

Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays

exposure

15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays.

limitations

Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed.

nutrient_topic

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

organism

Homo sapiens

plain_language

This high-concentration exposure impaired respiratory complex I in the studied cancer cells.

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 cell cultures

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1341–1353

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays · source_derived_draft · unverified_draft

### c-reg-complex-i-inactivation After 15 pmol/cell (approximately 8 mM) ascorbate for 1 h, NSCLC lysates showed reduced respiratory-complex I activity while the separately assayed complex IV activity was retained, consistent with vulnerability of Fe-S-containing machinery. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: This high-concentration exposure impaired respiratory complex I in the studied cancer cells. organism: Homo sapiens tissue_or_cell_type: NSCLC cell cultures experimental_model: Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays limitations: Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed. exposure: 15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays. cross_nutrient: true evidence_location: Figure 6D [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

false

evidence_location

Abstract, later phenotypic changes

experimental_model

Mitochondrial ACP siRNA in HEK293T cells

exposure

ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown.

limitations

Temporal ordering alone does not separate all direct complex-I effects from secondary cellular injury; abstract-level extraction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

The carrier-protein defect also impaired complex I function.

primary_references

[b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200

tissue_or_cell_type

HEK293T mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 837–849

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial ACP siRNA in HEK293T cells · source_derived_draft · unverified_draft

### b5-met-mtacp-complex-i Mitochondrial ACP knockdown in HEK293T cells subsequently reduced respiratory complex I specific activity. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier-protein defect also impaired complex I function. organism: Homo sapiens tissue_or_cell_type: HEK293T mitochondria experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Temporal ordering alone does not separate all direct complex-I effects from secondary cellular injury; abstract-level extraction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown. cross_nutrient: false evidence_location: Abstract, later phenotypic changes [b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"}

experimental_model

COA6 knockout HEK293T cells and biochemical protein interaction experiments

exposure

COA6 loss; SCO1/SCO2 disulfide reduction assays

limitations

COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import.

nutrient_topic

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

organism

Human cells and proteins

plain_language

A failure in copper-enzyme assembly can affect more than one respiratory complex.

primary_references

[copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036

tissue_or_cell_type

Mitochondrial intermembrane space

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 676–687

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · COA6 knockout HEK293T cells and biochemical protein interaction experiments · source_derived_draft · unverified_draft

### copper-coa6-respiratory-loss COA6 loss caused combined respiratory complex I and IV deficiency in human cells. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A failure in copper-enzyme assembly can affect more than one respiratory complex. organism: Human cells and proteins tissue_or_cell_type: Mitochondrial intermembrane space experimental_model: COA6 knockout HEK293T cells and biochemical protein interaction experiments limitations: COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import. exposure: COA6 loss; SCO1/SCO2 disulfide reduction assays evidence_span: {"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"} [copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036

evidence_span

{"source_cache": "artifacts/metformin-research/24843020.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae", "start_char": 0, "end_char": 1142, "text_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae"}

experimental_model

Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue

exposure

Metformin in the presence and absence of glucose; NDI1 overexpression

limitations

Cancer-cell concentrations are far above therapeutic plasma levels. The NDI1 rescue is strong evidence that the effects run through complex I in this model, not evidence of an antitumour indication.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human cells; mouse in vivo

plain_language

The drug slows the first station of the mitochondrial energy chain.

primary_references

[metformin-p24843020] Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24843020/ DOI: 10.7554/elife.02242

tissue_or_cell_type

Cancer cells and tumours

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 385–396

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue · source_derived_draft · unverified_draft

### metformin-complex-i-inhibition Metformin inhibited mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration in human cancer cells. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The drug slows the first station of the mitochondrial energy chain. organism: Human cells; mouse in vivo tissue_or_cell_type: Cancer cells and tumours experimental_model: Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue limitations: Cancer-cell concentrations are far above therapeutic plasma levels. The NDI1 rescue is strong evidence that the effects run through complex I in this model, not evidence of an antitumour indication. exposure: Metformin in the presence and absence of glucose; NDI1 overexpression evidence_span: {"source_cache": "artifacts/metformin-research/24843020.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae", "start_char": 0, "end_char": 1142, "text_sha256": "21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae"} [metformin-p24843020] Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24843020/ DOI: 10.7554/elife.02242

evidence_span

{"source_cache": "artifacts/metformin-research/15047621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6", "start_char": 0, "end_char": 1613, "text_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6"}

experimental_model

Tissue homogenates, isolated mitochondria and intact rat soleus muscle

exposure

Metformin 30 mmol/l in homogenates and 270 micromol/l for 24 h in intact muscle, compared with thiazolidinediones

limitations

Millimolar concentrations in homogenates are far above therapeutic exposure. The comparison drugs are included because the paper measured them together, not as a metformin claim.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Rat tissue and isolated mitochondria

plain_language

The block is specific to the first complex; feeding the chain past it restores respiration.

primary_references

[metformin-p15047621] Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? (2004). https://pubmed.ncbi.nlm.nih.gov/15047621/ DOI: 10.2337/diabetes.53.4.1052

tissue_or_cell_type

Skeletal muscle

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 437–448

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tissue homogenates, isolated mitochondria and intact rat soleus muscle · source_derived_draft · unverified_draft

### metformin-complex-i-muscle Metformin reduced complex I activity in skeletal-muscle homogenates and reduced state 3 respiration of isolated mitochondria consuming glutamate and malate, while respiration on succinate through complex II was unaffected. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The block is specific to the first complex; feeding the chain past it restores respiration. organism: Rat tissue and isolated mitochondria tissue_or_cell_type: Skeletal muscle experimental_model: Tissue homogenates, isolated mitochondria and intact rat soleus muscle limitations: Millimolar concentrations in homogenates are far above therapeutic exposure. The comparison drugs are included because the paper measured them together, not as a metformin claim. exposure: Metformin 30 mmol/l in homogenates and 270 micromol/l for 24 h in intact muscle, compared with thiazolidinediones evidence_span: {"source_cache": "artifacts/metformin-research/15047621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6", "start_char": 0, "end_char": 1613, "text_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6"} [metformin-p15047621] Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? (2004). https://pubmed.ncbi.nlm.nih.gov/15047621/ DOI: 10.2337/diabetes.53.4.1052

dose

Annonacin concentration series

duration

48 hours

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Primary rat striatal neurons

limitations

Purified-cell exposure establishes a hazard mechanism, not the dose delivered to human neurons by a particular graviola food.

nutrient_topic

Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata

organism

Primary rat striatal neurons

plain_language

Annonacin inhibited mitochondrial complex-I-linked energy production, producing a concentration-dependent ATP fall, tau redistribution and death in cultured rat striatal neurons.

primary_references

Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007

route

In vitro

tissue

ATP, mitochondrial transport, tau localization and cell death

Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 44–53

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary rat striatal neurons · source_derived_draft · unverified_draft

## graviola-complex1-atp Annonacin inhibited mitochondrial complex-I-linked energy production, producing a concentration-dependent ATP fall, tau redistribution and death in cultured rat striatal neurons. Model/species: Primary rat striatal neurons Tissue/system: ATP, mitochondrial transport, tau localization and cell death Exposure: Annonacin concentration series Route: In vitro Duration: 48 hours Limits: Purified-cell exposure establishes a hazard mechanism, not the dose delivered to human neurons by a particular graviola food. Primary reference: Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Annonacin with NDI1 expression, glycolysis stimulation or antioxidants

duration

48 hours

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Primary rat striatal neurons

limitations

NDI1 is an experimental bypass, and lack of antioxidant rescue does not exclude every redox contribution in vivo.

nutrient_topic

Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata

organism

Primary rat striatal neurons

plain_language

Forced yeast NDI1 expression or stimulation of anaerobic glycolysis prevented annonacin-associated tau redistribution and neuronal death, whereas antioxidants did not.

primary_references

Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007

route

In vitro perturbation

tissue

Energy-pathway rescue and antioxidant controls

trigger_kind

machinery_impairment Imported condition classification; unverified.

Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 55–64

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary rat striatal neurons · source_derived_draft · unverified_draft

## graviola-ndi1-rescue Forced yeast NDI1 expression or stimulation of anaerobic glycolysis prevented annonacin-associated tau redistribution and neuronal death, whereas antioxidants did not. Model/species: Primary rat striatal neurons Tissue/system: Energy-pathway rescue and antioxidant controls Exposure: Annonacin with NDI1 expression, glycolysis stimulation or antioxidants Route: In vitro perturbation Duration: 48 hours Limits: NDI1 is an experimental bypass, and lack of antioxidant rescue does not exclude every redox contribution in vivo. Primary reference: Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"}

experimental_model

Patient-derived cell biochemistry and variant structural analysis

exposure

Compound-heterozygous GLRX5 variants

limitations

One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.

nutrient_topic

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

organism

Human GLRX5-deficient patient

plain_language

The defect extended beyond red-cell pigment to mitochondrial energy handling.

primary_references

[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012

tissue_or_cell_type

Lymphoblastoid and CD34-positive cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1096–1107

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived cell biochemistry and variant structural analysis · source_derived_draft · unverified_draft

### iron-glrx5-energy Patient-derived cells showed reduced glutathione and aconitase activity, damaged/depleted mitochondrial DNA, lower complex I/IV activities and lower ATP content. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect extended beyond red-cell pigment to mitochondrial energy handling. organism: Human GLRX5-deficient patient tissue_or_cell_type: Lymphoblastoid and CD34-positive cells experimental_model: Patient-derived cell biochemistry and variant structural analysis limitations: One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated. exposure: Compound-heterozygous GLRX5 variants evidence_span: {"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"} [iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Full text lines 49–55; Fig. 3; Supplementary Figs. S6–S10

experimental_model

Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria

exposure

Cardiac-specific genetic deletion; 6- and 16-week assembly assays, 6- and 10-week respiratory assays.

limitations

The FeS subunits of complexes II/III were preferentially affected, whereas broader complex-I subunit loss supports an additional assembly role. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Mus musculus

plain_language

Loss of the carrier impaired assembly of several respiratory complexes in mouse heart.

primary_references

[b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x

tissue_or_cell_type

Heart mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 949–961

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria · source_derived_draft · unverified_draft

### b5-met-heart-acp-complex-assembly Cardiac Ndufab1 deletion reduced assembled respiratory complexes I–III and supercomplexes in mouse heart mitochondria. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of the carrier impaired assembly of several respiratory complexes in mouse heart. organism: Mus musculus tissue_or_cell_type: Heart mitochondria experimental_model: Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria limitations: The FeS subunits of complexes II/III were preferentially affected, whereas broader complex-I subunit loss supports an additional assembly role. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Cardiac-specific genetic deletion; 6- and 16-week assembly assays, 6- and 10-week respiratory assays. cross_nutrient: true evidence_location: Full text lines 49–55; Fig. 3; Supplementary Figs. S6–S10 [b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Full text lines 47–49; Fig. 3A

experimental_model

Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria

exposure

Cardiac-specific genetic deletion; 6- and 16-week assembly assays, 6- and 10-week respiratory assays.

limitations

Isolated-mitochondria oxygen consumption does not measure nutrient absorption or human exercise capacity. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Mus musculus

plain_language

The respiratory defect affected several upstream electron-transfer routes but spared the tested complex IV route.

primary_references

[b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x

tissue_or_cell_type

Heart mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 963–975

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria · source_derived_draft · unverified_draft

### b5-met-heart-acp-respiration Cardiac Ndufab1 deletion lowered oxygen consumption supported by complex I-, II-, or III-linked substrates, while complex IV-linked respiration remained unchanged. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The respiratory defect affected several upstream electron-transfer routes but spared the tested complex IV route. organism: Mus musculus tissue_or_cell_type: Heart mitochondria experimental_model: Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria limitations: Isolated-mitochondria oxygen consumption does not measure nutrient absorption or human exercise capacity. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Cardiac-specific genetic deletion; 6- and 16-week assembly assays, 6- and 10-week respiratory assays. cross_nutrient: false evidence_location: Full text lines 47–49; Fig. 3A [b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x