Mitochondrial protein lipoylation

evidence_span

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experimental_model

Purified enzymes and bacterial pathway reconstruction

exposure

Recombinant proteins and radiolabeled substrates

limitations

Bacterial complementation; the purified donor-transfer assay used mouse Lipt2. This is not direct flux measurement in a human mitochondrion.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human proteins; mouse Lipt2 in purified transfer assays; E. coli host

plain_language

Human LIPT2 restored the missing pathway function in a bacterial test.

primary_references

[ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115

tissue_or_cell_type

Lipoyl assembly pathway

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 234–245

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes and bacterial pathway reconstruction · source_derived_draft · unverified_draft

### ala-human-lipt2-complementation Full-length human LIPT2 complemented the E. coli lipB/lplA deletion strain, supporting its octanoyltransferase assignment. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human LIPT2 restored the missing pathway function in a bacterial test. organism: Human proteins; mouse Lipt2 in purified transfer assays; E. coli host tissue_or_cell_type: Lipoyl assembly pathway experimental_model: Purified enzymes and bacterial pathway reconstruction limitations: Bacterial complementation; the purified donor-transfer assay used mouse Lipt2. This is not direct flux measurement in a human mitochondrion. exposure: Recombinant proteins and radiolabeled substrates evidence_span: {"source_cache": "artifacts/ala-research/29987032.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0569075b59128ea021be6077596127d1c7aae1f9ac6b0acfd2ebcb268b650d3", "start_char": 31198, "end_char": 31564, "text_sha256": "967fbdc21edbac2bfd27e7c9c92a2ffe8a0b167c96d55f1095e429241be9463f"} [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Affected patient, biochemical testing and complementation

exposure

Compound-heterozygous LIPT1 variants

limitations

Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human

plain_language

The cofactor was not reaching the dehydrogenase machinery.

primary_references

[ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585

tissue_or_cell_type

Patient-derived cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 455–466

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected patient, biochemical testing and complementation · source_derived_draft · unverified_draft

### ala-lipt1-e2-loss The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor was not reaching the dehydrogenase machinery. organism: Human tissue_or_cell_type: Patient-derived cells experimental_model: Affected patient, biochemical testing and complementation limitations: Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency. exposure: Compound-heterozygous LIPT1 variants evidence_span: {"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"} [ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"}

experimental_model

Three affected children from two families and patient-derived fibroblasts

exposure

Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation

limitations

Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human

plain_language

Repairing the assembly enzyme restored attachment of the cofactor.

primary_references

[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001

tissue_or_cell_type

Patient cells and clinical phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 416–427

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three affected children from two families and patient-derived fibroblasts · source_derived_draft · unverified_draft

### ala-lipt2-lipoylation-loss Patient LIPT2 defects reduced mitochondrial protein lipoylation; wild-type LIPT2 expression restored it. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Repairing the assembly enzyme restored attachment of the cofactor. organism: Human tissue_or_cell_type: Patient cells and clinical phenotype experimental_model: Three affected children from two families and patient-derived fibroblasts limitations: Rare inherited disease; not evidence for common dietary lipoic-acid deficiency. exposure: Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation evidence_span: {"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"} [ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"}

experimental_model

Engineered bacterial ligase in human knockout cells and a modeled patient allele

exposure

Mitochondrially targeted engineered LplA expression

limitations

Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human cells with bacterial enzyme engineering

plain_language

Adding a new enzyme created a route that free supplementation alone did not supply.

primary_references

[ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995

tissue_or_cell_type

Lipoylation-null cell models and K562 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 559–570

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered bacterial ligase in human knockout cells and a modeled patient allele · source_derived_draft · unverified_draft

### ala-lpla-lipoylation-rescue Engineered LplA restored lipoylation in MECR-, BOLA3-, FDX1-, LIAS- and LIPT1-knockout cell models. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding a new enzyme created a route that free supplementation alone did not supply. organism: Human cells with bacterial enzyme engineering tissue_or_cell_type: Lipoylation-null cell models and K562 cells experimental_model: Engineered bacterial ligase in human knockout cells and a modeled patient allele limitations: Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial. exposure: Mitochondrially targeted engineered LplA expression evidence_span: {"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"} [ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Two families with Fe-S disorders and fibroblast gene complementation

exposure

NFU1 and BOLA3 pathogenic variants; isoform-specific rescue

limitations

Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human

plain_language

The cofactor pathway depends on correctly assembled iron-sulfur machinery.

primary_references

[ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011

tissue_or_cell_type

Fibroblasts and mitochondrial enzymes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 507–518

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two families with Fe-S disorders and fibroblast gene complementation · source_derived_draft · unverified_draft

### ala-nfu1-patient-defect The reported NFU1 splice-disrupting variant eliminated detectable mature mitochondrial NFU1 and accompanied lipoate-synthesis and 2-oxoacid dehydrogenase defects. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor pathway depends on correctly assembled iron-sulfur machinery. organism: Human tissue_or_cell_type: Fibroblasts and mitochondrial enzymes experimental_model: Two families with Fe-S disorders and fibroblast gene complementation limitations: Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction. exposure: NFU1 and BOLA3 pathogenic variants; isoform-specific rescue evidence_span: {"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"} [ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"}

experimental_model

Variant nonketotic hyperglycinemia cohort and cell complementation

exposure

LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells

limitations

Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human

plain_language

Delivering the molecule nearer mitochondria was still insufficient in these models.

primary_references

[ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328

tissue_or_cell_type

Eight genetically explained patients within an eleven-person group

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 546–557

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Variant nonketotic hyperglycinemia cohort and cell complementation · source_derived_draft · unverified_draft

### ala-variant-lipoate-no-rescue Neither lipoate nor mitochondrially targeted lipoate corrected the studied cellular lipoylation deficiency. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delivering the molecule nearer mitochondria was still insufficient in these models. organism: Human tissue_or_cell_type: Eight genetically explained patients within an eleven-person group experimental_model: Variant nonketotic hyperglycinemia cohort and cell complementation limitations: Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders. exposure: LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells evidence_span: {"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"} [ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Full text line 47; Supplementary Fig. S4B

experimental_model

Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria

exposure

Cardiomyocyte-specific Ndufab1 deletion.

limitations

A null result for these measurements is not proof that all fatty-acid synthesis was intact. Different tissue, developmental timing and depletion conditions preclude a same-context contradiction with HEK293T cells. 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

Mouse heart respiratory failure occurred without the measured lipoylation defect seen in the cultured-cell study.

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 977–989

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-lipoylation-spared In the cardiac Ndufab1-knockout study, the measured mitochondrial protein lipoylation was not significantly changed despite respiratory defects. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse heart respiratory failure occurred without the measured lipoylation defect seen in the cultured-cell study. organism: Mus musculus tissue_or_cell_type: Heart mitochondria experimental_model: Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria limitations: A null result for these measurements is not proof that all fatty-acid synthesis was intact. Different tissue, developmental timing and depletion conditions preclude a same-context contradiction with HEK293T cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Cardiomyocyte-specific Ndufab1 deletion. cross_nutrient: true evidence_location: Full text line 47; Supplementary Fig. S4B [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

true

evidence_location

Abstract, lipoic-acid supplementation result

experimental_model

Mitochondrial ACP siRNA in HEK293T cells

exposure

Lipoic-acid supplementation of ACP-knockdown cultures; concentration not extracted.

limitations

Lipoic acid offered some oxidative-damage protection, but that is a different endpoint; result is not a universal statement about every lipoylation disorder. 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

External lipoic acid did not bypass this carrier-protein defect.

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 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 851–863

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-lipoate-nonrescue Adding lipoic acid to the culture medium did not reverse the protein-lipoylation defect caused by mitochondrial ACP knockdown in HEK293T cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: External lipoic acid did not bypass this carrier-protein defect. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Lipoic acid offered some oxidative-damage protection, but that is a different endpoint; result is not a universal statement about every lipoylation disorder. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Lipoic-acid supplementation of ACP-knockdown cultures; concentration not extracted. cross_nutrient: true evidence_location: Abstract, lipoic-acid supplementation result [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.

cross_nutrient

true

evidence_location

Abstract, earliest phenotypic changes; Fig. 2 caption

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

Antibody-based lipoylation readout; not a measurement of dietary lipoic acid or pantothenate shortage. 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

Loss of the mitochondrial carrier impaired attachment of the lipoate cofactor to proteins.

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 mitochondrial proteins

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 823–835

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-lipoylation Mitochondrial ACP knockdown in HEK293T cells reduced the proportion of mitochondrial proteins recognized as lipoylated before later respiratory defects. 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 mitochondrial carrier impaired attachment of the lipoate cofactor to proteins. organism: Homo sapiens tissue_or_cell_type: HEK293T mitochondrial proteins experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Antibody-based lipoylation readout; not a measurement of dietary lipoic acid or pantothenate shortage. 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: true evidence_location: Abstract, earliest phenotypic changes; Fig. 2 caption [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

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experimental_model

Two families with Fe-S disorders and fibroblast gene complementation

exposure

NFU1 and BOLA3 pathogenic variants; isoform-specific rescue

limitations

Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human

plain_language

The intact cell needs BOLA3 even though its precise role differs from a purified donor assay.

primary_references

[ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011

tissue_or_cell_type

Fibroblasts and mitochondrial enzymes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 520–531

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two families with Fe-S disorders and fibroblast gene complementation · source_derived_draft · unverified_draft

### ala-bola3-patient-defect BOLA3 deficiency caused combined respiratory and 2-oxoacid dehydrogenase defects; expression of the appropriate BOLA3 isoform restored function. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intact cell needs BOLA3 even though its precise role differs from a purified donor assay. organism: Human tissue_or_cell_type: Fibroblasts and mitochondrial enzymes experimental_model: Two families with Fe-S disorders and fibroblast gene complementation limitations: Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction. exposure: NFU1 and BOLA3 pathogenic variants; isoform-specific rescue evidence_span: {"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"} [ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011