Component

Mouse mitochondrial trifunctional protein alpha subunit / Hadha

Study-specific entity. Experimental conditions and evidence limits remain on each linked claim.

5 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. Mouse cardiac Dlat and HADHA co-immunoprecipitated; their association was stronger in the HFpEF model.

    Mouse dihydrolipoyl acetyltransferase / Dlat → Mouse mitochondrial trifunctional protein alpha subunit / Hadha source_derived_draftungraded
    Experimental context and source evidence
    access_level
    full_text_and_supplement_review
    compartment
    Cardiac tissue / mitochondria
    dose
    Two-hit model: 60% fat-calorie diet and L-NAME 0.5 g/L drinking water; vector dose not reported in reviewed text
    duration
    Two-hit protocol 15 weeks. Transgenic age/induction wording differs across passages; do not infer one exact interval
    endpoint
    mouse-hadha
    evidence_location
    Reciprocal co-immunoprecipitation; Figure 6D/E/H
    experimental_model
    Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated
    exposure
    mouse-dlat
    limitations
    Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Co-immunoprecipitation establishes association, not by itself direct binding or acetyl transfer.
    organism
    Mus musculus
    plain_language
    Mouse cardiac Dlat and HADHA co-immunoprecipitated; their association was stronger in the HFpEF model.
    primary_locator
    [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}]
    primary_references
    https://doi.org/10.1038/s41467-026-70703-w
    sample_size
    6 per group
    tissue_or_cell_type
    Cardiac tissue and cardiomyocytes

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 16–31

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft

    Mouse cardiac Dlat and HADHA co-immunoprecipitated; their association was stronger in the HFpEF model. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: Two-hit model: 60% fat-calorie diet and L-NAME 0.5 g/L drinking water; vector dose not reported in reviewed text duration: Two-hit protocol 15 weeks. Transgenic age/induction wording differs across passages; do not infer one exact interval primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Reciprocal co-immunoprecipitation; Figure 6D/E/H endpoint: mouse-hadha exposure: mouse-dlat limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Co-immunoprecipitation establishes association, not by itself direct binding or acetyl transfer. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}] plain_language: Mouse cardiac Dlat and HADHA co-immunoprecipitated; their association was stronger in the HFpEF model. sample_size: 6 per group
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Cardiac Dlat overexpression increased HADHA acetylation without a corresponding significant change in HADHA abundance.

    Cardiomyocyte-specific mouse Dlat overexpression → Mouse cardiac HADHA lysine acetylation source_derived_draftungraded
    Experimental context and source evidence
    access_level
    full_text_and_supplement_review
    compartment
    Cardiac tissue / mitochondria
    dose
    Tamoxifen-induced genetic overexpression; vector/induction dose not established in this extraction
    duration
    Transgenic induction age and observation interval differ across passages; exact interval unresolved
    endpoint
    mouse-hadha-acetylation
    evidence_location
    HADHA IP/immunoblot; Figure 6I
    experimental_model
    Conditional cardiac Dlat-transgenic mice; HADHA AAV9 rescue where stated
    exposure
    mouse-dlat-overexpression
    limitations
    Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects.
    organism
    Mus musculus
    plain_language
    Cardiac Dlat overexpression increased HADHA acetylation without a corresponding significant change in HADHA abundance.
    primary_locator
    [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}]
    primary_references
    https://doi.org/10.1038/s41467-026-70703-w
    sample_size
    4 biological replicates
    tissue_or_cell_type
    Cardiac tissue and cardiomyocytes

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 335–350

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Conditional cardiac Dlat-transgenic mice; HADHA AAV9 rescue where stated · source_derived_draft · unverified_draft

    Cardiac Dlat overexpression increased HADHA acetylation without a corresponding significant change in HADHA abundance. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Conditional cardiac Dlat-transgenic mice; HADHA AAV9 rescue where stated compartment: Cardiac tissue / mitochondria dose: Tamoxifen-induced genetic overexpression; vector/induction dose not established in this extraction duration: Transgenic induction age and observation interval differ across passages; exact interval unresolved primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: HADHA IP/immunoblot; Figure 6I endpoint: mouse-hadha-acetylation exposure: mouse-dlat-overexpression limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}] plain_language: Cardiac Dlat overexpression increased HADHA acetylation without a corresponding significant change in HADHA abundance. sample_size: 4 biological replicates
    Complete structured claim and evidence

  2. AAV9-mediated HADHA overexpression restored FAO-associated respiration in Dlat-transgenic mouse hearts.

    Cardiomyocyte-targeted mouse HADHA overexpression → Mouse cardiac fatty-acid oxidation capacity source_derived_draftungraded
    Experimental context and source evidence
    access_level
    full_text_and_supplement_review
    compartment
    Cardiac tissue / mitochondria
    dose
    Tamoxifen-induced genetic overexpression; vector/induction dose not established in this extraction
    duration
    Transgenic induction age and observation interval differ across passages; exact interval unresolved
    endpoint
    mouse-cardiac-fao
    evidence_location
    Supplementary Figure S21
    experimental_model
    Conditional cardiac Dlat-transgenic mice; HADHA AAV9 rescue where stated
    exposure
    mouse-hadha-overexpression
    limitations
    Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Wild-type HADHA overexpression, not a K728R mouse rescue; increased enzyme abundance does not isolate the acetylation-site mechanism.
    organism
    Mus musculus
    plain_language
    AAV9-mediated HADHA overexpression restored FAO-associated respiration in Dlat-transgenic mouse hearts.
    primary_locator
    [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 52, "text_sha256": "74297778077d895148e1cc0c9819297c22c274b0ec6fdce0483ce8ba94ab58b4", "xml_element_id": "Par21"}]
    primary_references
    https://doi.org/10.1038/s41467-026-70703-w
    sample_size
    4 biological replicates
    tissue_or_cell_type
    Cardiac tissue and cardiomyocytes

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 477–492

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Conditional cardiac Dlat-transgenic mice; HADHA AAV9 rescue where stated · source_derived_draft · unverified_draft

    AAV9-mediated HADHA overexpression restored FAO-associated respiration in Dlat-transgenic mouse hearts. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Conditional cardiac Dlat-transgenic mice; HADHA AAV9 rescue where stated compartment: Cardiac tissue / mitochondria dose: Tamoxifen-induced genetic overexpression; vector/induction dose not established in this extraction duration: Transgenic induction age and observation interval differ across passages; exact interval unresolved primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Supplementary Figure S21 endpoint: mouse-cardiac-fao exposure: mouse-hadha-overexpression limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Wild-type HADHA overexpression, not a K728R mouse rescue; increased enzyme abundance does not isolate the acetylation-site mechanism. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 52, "text_sha256": "74297778077d895148e1cc0c9819297c22c274b0ec6fdce0483ce8ba94ab58b4", "xml_element_id": "Par21"}] plain_language: AAV9-mediated HADHA overexpression restored FAO-associated respiration in Dlat-transgenic mouse hearts. sample_size: 4 biological replicates
    Complete structured claim and evidence

  3. Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts.

    Nicotinamide riboside → Mouse cardiac HADHA lysine acetylation source_derived_draftungraded
    Experimental context and source evidence
    access_level
    full_text_and_supplement_review
    compartment
    Cardiac tissue / mitochondria
    dose
    400 mg/kg/day
    duration
    Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative
    endpoint
    mouse-hadha-acetylation
    evidence_location
    IP/immunoblot; Figure 2L
    experimental_model
    Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated
    exposure
    nicotinamide-riboside
    limitations
    Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The experiment does not establish selective direct NR action on HADHA or prove SIRT3 is the only mediator.
    nutrient_topic
    Topical cross-reference only; no inheritance of another actor's effects. · NAD+
    organism
    Mus musculus
    plain_language
    Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts.
    primary_locator
    [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}]
    primary_references
    https://doi.org/10.1038/s41467-026-70703-w
    route
    Oral gavage
    sample_size
    3 per group
    tissue_or_cell_type
    Cardiac tissue and cardiomyocytes

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 532–548

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft

    Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: IP/immunoblot; Figure 2L endpoint: mouse-hadha-acetylation exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The experiment does not establish selective direct NR action on HADHA or prove SIRT3 is the only mediator. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts. sample_size: 3 per group
    Complete structured claim and evidence

  4. Spermidine increased the HADHA-attributed activity readout in mouse cardiac lysates from treated animals.

    Spermidine → HADHA-attributed activity in lysate assay source_derived_draftungraded
    Experimental context and source evidence
    access_level
    full_text_and_supplement_review
    compartment
    Cardiac tissue / mitochondria
    dose
    30 mM in drinking water, as reported
    duration
    10 weeks in the Results; broader two-hit methods specify 15 weeks
    endpoint
    hadha-attributed-lysate-activity
    evidence_location
    Figure 8A/B
    experimental_model
    Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated
    exposure
    spermidine
    limitations
    Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. This paper does not itself establish direct spermidine binding; that statement cites earlier work. Do not infer intake in mg/kg from water concentration. Lysate specificity/protocol units remain qualified.
    nutrient_topic
    Topical cross-reference only; no inheritance of another actor's effects. · Spermidine
    organism
    Mus musculus
    plain_language
    Spermidine increased the HADHA-attributed activity readout in mouse cardiac lysates from treated animals.
    primary_locator
    [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 54, "text_sha256": "ecfe210aa0338ec52935a354f2bcc46289d65981b7b09fd4299e4e4f2fac4254", "xml_element_id": "Par22"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 56, "text_sha256": "b4baf8321f41630eff2d66a4181f2907f674041d430ba7878fd278f33d4141cf", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 102, "text_sha256": "299ae9af6e500af03d85d3cc327c60cb04e94f0618b6a9910780ac928e42faff", "xml_element_id": "Par46"}]
    primary_references
    https://doi.org/10.1038/s41467-026-70703-w
    route
    Drinking water
    sample_size
    4 per group
    tissue_or_cell_type
    Cardiac tissue and cardiomyocytes

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 641–657

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft

    Spermidine increased the HADHA-attributed activity readout in mouse cardiac lysates from treated animals. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 30 mM in drinking water, as reported duration: 10 weeks in the Results; broader two-hit methods specify 15 weeks route: Drinking water primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Figure 8A/B endpoint: hadha-attributed-lysate-activity exposure: spermidine limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. This paper does not itself establish direct spermidine binding; that statement cites earlier work. Do not infer intake in mg/kg from water concentration. Lysate specificity/protocol units remain qualified. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 54, "text_sha256": "ecfe210aa0338ec52935a354f2bcc46289d65981b7b09fd4299e4e4f2fac4254", "xml_element_id": "Par22"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 56, "text_sha256": "b4baf8321f41630eff2d66a4181f2907f674041d430ba7878fd278f33d4141cf", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 102, "text_sha256": "299ae9af6e500af03d85d3cc327c60cb04e94f0618b6a9910780ac928e42faff", "xml_element_id": "Par46"}] plain_language: Spermidine increased the HADHA-attributed activity readout in mouse cardiac lysates from treated animals. sample_size: 4 per group
    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