Component

Mouse activating transcription factor 4 / Atf4

Context-specific entity; species, compartment and exposure are stated on each claim.

6 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 it acts on

  1. The study linked ATF4-dependent stress signaling to increased hepatic Gpt2 expression in the examined mouse ER-stress and obesity settings.

    Mouse activating transcription factor 4 / Atf4 → Mouse mitochondrial alanine aminotransferase / Gpt2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse hepatocyte/liver interventions and expression assays.
    limitations
    Expression regulation is context-specific and does not establish a human supplementation response. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    Stress can change how much alanine-processing enzyme a liver expresses.
    primary_references
    Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 224–230

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse hepatocyte/liver interventions and expression assays. · source_derived_draft · unverified_draft

    ## alanine-liver-atf4 Stress can change how much alanine-processing enzyme a liver expresses. The study linked ATF4-dependent stress signaling to increased hepatic Gpt2 expression in the examined mouse ER-stress and obesity settings. Model: Mouse hepatocyte/liver interventions and expression assays. Limitations: Expression regulation is context-specific and does not establish a human supplementation response. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
    Complete structured claim and evidence

  2. ATF4 siRNA reduced the fisetin-associated basal glutathione increase; Nrf2 siRNA did not have the same basal requirement.

    Mouse activating transcription factor 4 / Atf4 → Mouse-cell basal glutathione response to fisetin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse-cell transcription-factor silencing.
    limitations
    Baseline and oxidative-stress settings are distinct.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    Baseline glutathione regulation depended more on ATF4.
    primary_references
    Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 120–126

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-cell transcription-factor silencing. · source_derived_draft · unverified_draft

    ## fisetin-atf4-basal-dependence Baseline glutathione regulation depended more on ATF4. ATF4 siRNA reduced the fisetin-associated basal glutathione increase; Nrf2 siRNA did not have the same basal requirement. Model: Mouse-cell transcription-factor silencing. Limitations: Baseline and oxidative-stress settings are distinct. Evidence access: Primary abstract Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010
    Complete structured claim and evidence

What acts on it

  1. ATF4 protein increased after three hours of T-cell activation in dialyzed-serum medium and returned toward control with alanine supplementation.

    L-Alanine → Mouse activating transcription factor 4 / Atf4 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back.
    limitations
    ATF4 measurement supports a stress response; direct GCN2 necessity was not established in this experiment.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    Amino-acid stress signaling responded when alanine was restored.
    primary_references
    T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 112–118

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. · source_derived_draft · unverified_draft

    ## alanine-t-cell-stress Amino-acid stress signaling responded when alanine was restored. ATF4 protein increased after three hours of T-cell activation in dialyzed-serum medium and returned toward control with alanine supplementation. Model: Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. Limitations: ATF4 measurement supports a stress response; direct GCN2 necessity was not established in this experiment. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
    Complete structured claim and evidence

  2. Fisetin increased ATF4 stability through a kinase-dependent process in the mouse-cell study.

    Fisetin → Mouse activating transcription factor 4 / Atf4 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Protein-stability and kinase-perturbation experiments.
    limitations
    Kinase dependence does not identify one specific kinase.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    A second regulator contributes through a different mechanism.
    primary_references
    Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 112–118

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Protein-stability and kinase-perturbation experiments. · source_derived_draft · unverified_draft

    ## fisetin-atf4-stability A second regulator contributes through a different mechanism. Fisetin increased ATF4 stability through a kinase-dependent process in the mouse-cell study. Model: Protein-stability and kinase-perturbation experiments. Limitations: Kinase dependence does not identify one specific kinase. Evidence access: Primary abstract Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010
    Complete structured claim and evidence

  3. Under oxidative stress, siRNA experiments implicated both Nrf2 and ATF4 in the mouse-cell glutathione response to fisetin.

    Mouse Nrf2 / Nfe2l2 → Mouse activating transcription factor 4 / Atf4 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse-cell gene-silencing comparisons.
    limitations
    Cooperation in this assay is not proof of universal transcriptional synergy.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    The cell relies on both regulators during stress.
    primary_references
    Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 128–134

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-cell gene-silencing comparisons. · source_derived_draft · unverified_draft

    ## fisetin-stress-cooperation The cell relies on both regulators during stress. Under oxidative stress, siRNA experiments implicated both Nrf2 and ATF4 in the mouse-cell glutathione response to fisetin. Model: Mouse-cell gene-silencing comparisons. Limitations: Cooperation in this assay is not proof of universal transcriptional synergy. Evidence access: Primary abstract Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. In mouse HT22 cells, added iron reduced fisetin-induced nuclear Nrf2 and ATF4 from an iron:fisetin ratio of 0.5:1; copper did not do so in the tested range.

    Ferrous iron → Mouse Nrf2 / Nfe2l2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    5 micromolar fisetin with FeCl2/CuCl2 titration.
    limitations
    Cell-culture ratio, not a clinical spacing rule for supplements.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    Iron weakened the signaling response under these conditions.
    primary_references
    Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 160–166

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 5 micromolar fisetin with FeCl2/CuCl2 titration. · source_derived_draft · unverified_draft

    ## fisetin-iron-signaling-antagonism Iron weakened the signaling response under these conditions. In mouse HT22 cells, added iron reduced fisetin-induced nuclear Nrf2 and ATF4 from an iron:fisetin ratio of 0.5:1; copper did not do so in the tested range. Model: 5 micromolar fisetin with FeCl2/CuCl2 titration. Limitations: Cell-culture ratio, not a clinical spacing rule for supplements. Evidence access: Primary full text Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113
    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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