Component

Mitochondrial complex I (NADH dehydrogenase) activity

Mitochondrial complex I (NADH dehydrogenase) activity. Species, exposure and limitations are retained in each linked claim.

3 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. Metformin inhibited mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration in human cancer cells.

    Metformin → Mitochondrial complex I (NADH dehydrogenase) activity 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
    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
    Complete structured claim and evidence

  2. 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.

    Metformin → Mitochondrial complex I (NADH dehydrogenase) activity source_derived_draftungraded
    Experimental context and source evidence
    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
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Dependency on complex I, and therefore sensitivity to metformin, was dictated by other pathways affecting NAD+ regeneration and aspartate levels, so sensitivity was not an intrinsic property of the cells.

    Metformin → Cellular NAD+/NADH ratio source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/metformin-research/27746050.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "661b69cac488b8ac530cc9385bff10b367b48327d01fe1c29c75bee56ee4f6b3", "start_char": 0, "end_char": 1079, "text_sha256": "661b69cac488b8ac530cc9385bff10b367b48327d01fe1c29c75bee56ee4f6b3"}
    experimental_model
    Cancer cells in varied culture environments with complex I inhibitors
    exposure
    Metformin and other complex I inhibitors across environments differing in NAD+ regeneration and aspartate supply
    limitations
    Establishes that sensitivity is environment-dependent; it argues against reading a culture concentration as a fixed drug property.
    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 and mouse cancer cells
    plain_language
    The same drug dose does different things depending on what else the cell can use.
    primary_references
    [metformin-p27746050] Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. (2016). https://pubmed.ncbi.nlm.nih.gov/27746050/ DOI: 10.1016/j.cmet.2016.09.006
    tissue_or_cell_type
    Cancer cells in culture and in vivo

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 723–734

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cancer cells in varied culture environments with complex I inhibitors · source_derived_draft · unverified_draft

    ### metformin-environment-sensitivity Dependency on complex I, and therefore sensitivity to metformin, was dictated by other pathways affecting NAD+ regeneration and aspartate levels, so sensitivity was not an intrinsic property of the 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 same drug dose does different things depending on what else the cell can use. organism: Human and mouse cancer cells tissue_or_cell_type: Cancer cells in culture and in vivo experimental_model: Cancer cells in varied culture environments with complex I inhibitors limitations: Establishes that sensitivity is environment-dependent; it argues against reading a culture concentration as a fixed drug property. exposure: Metformin and other complex I inhibitors across environments differing in NAD+ regeneration and aspartate supply evidence_span: {"source_cache": "artifacts/metformin-research/27746050.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "661b69cac488b8ac530cc9385bff10b367b48327d01fe1c29c75bee56ee4f6b3", "start_char": 0, "end_char": 1079, "text_sha256": "661b69cac488b8ac530cc9385bff10b367b48327d01fe1c29c75bee56ee4f6b3"} [metformin-p27746050] Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. (2016). https://pubmed.ncbi.nlm.nih.gov/27746050/ DOI: 10.1016/j.cmet.2016.09.006
    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.

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