Component

Mitochondrial cytochrome c oxidase / respiratory complex IV

Mitochondrial cytochrome c oxidase / respiratory complex IV. 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. COA6 loss caused combined respiratory complex I and IV deficiency in human cells.

    Human cytochrome c oxidase assembly factor COA6 → Mitochondrial cytochrome c oxidase / respiratory complex IV source_derived_draftungraded
    Experimental context and source evidence
    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
    Complete structured claim and evidence

  2. SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study.

    Human mitochondrial phosphate/copper carrier SLC25A3 → Mitochondrial cytochrome c oxidase / respiratory complex IV source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"}
    experimental_model
    Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes
    exposure
    SLC25A3 loss or reconstitution; extracellular copper addition
    limitations
    The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.
    nutrient_topic
    Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
    organism
    Human and mouse cells; heterologous yeast and Lactococcus assays
    plain_language
    Getting enough copper to the respiratory enzyme depends on transport machinery.
    primary_references
    [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
    tissue_or_cell_type
    Inner mitochondrial membrane
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 533–544

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes · source_derived_draft · unverified_draft

    ### copper-slc25a3-cox-deficiency SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Getting enough copper to the respiratory enzyme depends on transport machinery. organism: Human and mouse cells; heterologous yeast and Lactococcus assays tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes limitations: The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments. exposure: SLC25A3 loss or reconstitution; extracellular copper addition evidence_span: {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"} [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
    Complete structured claim and evidence

  3. Elesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells.

    Elesclomol-copper complex → Mitochondrial cytochrome c oxidase / respiratory complex IV source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"}
    experimental_model
    Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria
    exposure
    Slc25a3 deletion and elesclomol-copper exposure
    limitations
    Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.
    nutrient_topic
    Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
    organism
    Rat H9c2 cells; human SLC25A3 in Lactococcus lactis
    plain_language
    Delivering more copper to the organelle did not ensure delivery to the enzyme.
    primary_references
    [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
    tissue_or_cell_type
    Mitochondria; bacterial copper export assay
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Copper: transport, cuproenzymes, deficiency, excess 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 · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft

    ### copper-slc25a3-es-no-cox-rescue Elesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delivering more copper to the organelle did not ensure delivery to the enzyme. organism: Rat H9c2 cells; human SLC25A3 in Lactococcus lactis tissue_or_cell_type: Mitochondria; bacterial copper export assay experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Patient-derived cells showed reduced glutathione and aconitase activity, damaged/depleted mitochondrial DNA, lower complex I/IV activities and lower ATP content.

    Human mitochondrial glutaredoxin 5 / GLRX5 → ATP source_derived_draftungraded
    Experimental context and source evidence
    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
    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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