Component

Cellular mitochondrial respiration

Cellular mitochondrial respiration. Species, exposure and limitations are retained in each linked claim.

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

Read recorded mechanisms Open recursive mind map

How nutrients influence it

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

How nutrients reach it in more than one step

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

Tracing routes…

What it does

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

Recorded relationships

What acts on it

  1. BOLA3 deficiency caused combined respiratory and 2-oxoacid dehydrogenase defects; expression of the appropriate BOLA3 isoform restored function.

    Human BOLA3 → Cellular mitochondrial respiration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    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"}
    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
    Complete structured claim and evidence

  2. Cellular respiration fell with metformin, and cells relied exclusively on glycolysis for survival in its presence.

    Metformin → Cellular mitochondrial respiration source_derived_draftungraded
    Experimental context and source evidence
    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
    With the chain slowed, the cell falls back on the oxygen-free route.
    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 398–409

    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-respiration Cellular respiration fell with metformin, and cells relied exclusively on glycolysis for survival in its presence. 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: With the chain slowed, the cell falls back on the oxygen-free route. 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
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. LIPT2-deficient fibroblasts had reduced PDH and OGDH activities, oxygen consumption and leucine catabolic flux.

    Human octanoyltransferase / LIPT2 → Human pyruvate dehydrogenase complex source_derived_draftungraded
    Experimental context and source evidence
    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
    One early assembly failure disrupts carbohydrate and amino-acid processing.
    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 429–440

    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-multienzyme-failure LIPT2-deficient fibroblasts had reduced PDH and OGDH activities, oxygen consumption and leucine catabolic flux. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: One early assembly failure disrupts carbohydrate and amino-acid processing. 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
    Complete structured claim and evidence

  2. Engineered LplA restored cellular respiration and growth in low glucose in lipoylation-null cells, including a K562 model of a patient LIPT1 allele.

    Engineered bacterial LplA targeted to mammalian mitochondria → Growth of lipoylation-deficient cells in low glucose source_derived_draftungraded
    Experimental context and source evidence
    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
    The engineered bypass improved measured cellular function, not just a cofactor stain.
    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 572–583

    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-functional-rescue Engineered LplA restored cellular respiration and growth in low glucose in lipoylation-null cells, including a K562 model of a patient LIPT1 allele. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The engineered bypass improved measured cellular function, not just a cofactor stain. 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
    Complete structured claim and evidence

In the sources

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

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

    Evidence, AI assistance and curation standards