Component

Human mitochondrial threonyl-tRNA synthetase / TARS2

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

7 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. Human TARS2 generates mitochondrial Thr-tRNA Thr for mitochondrial translation.

    Human mitochondrial threonyl-tRNA synthetase / TARS2 → Human mitochondrial threonyl-tRNA Thr source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human TARS2 functional characterization and disease-variant assays.
    limitations
    Cytosolic TARS1 does not replace this mitochondrial record.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    Mitochondria have their own threonine-loading enzyme.
    primary_references
    Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 66–72

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TARS2 functional characterization and disease-variant assays. · source_derived_draft · unverified_draft

    ## l-threonine-tars2-charging Mitochondria have their own threonine-loading enzyme. Human TARS2 generates mitochondrial Thr-tRNA Thr for mitochondrial translation. Model: Human TARS2 functional characterization and disease-variant assays. Limitations: Cytosolic TARS1 does not replace this mitochondrial record. Evidence access: Primary abstract Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257
    Complete structured claim and evidence

  2. Human TARS2 clears mischarged Ser-tRNA Thr during mitochondrial translation.

    Human mitochondrial threonyl-tRNA synthetase / TARS2 → Mischarged human mitochondrial Ser-tRNA Thr source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human mitochondrial aminoacyl-tRNA synthetase biochemistry.
    limitations
    This is tRNA-bound substrate discrimination, not evidence that serine supplements cause mistranslation.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    Proofreading removes serine accidentally attached to threonine tRNA.
    primary_references
    Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 74–80

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human mitochondrial aminoacyl-tRNA synthetase biochemistry. · source_derived_draft · unverified_draft

    ## l-threonine-tars2-editing Proofreading removes serine accidentally attached to threonine tRNA. Human TARS2 clears mischarged Ser-tRNA Thr during mitochondrial translation. Model: Human mitochondrial aminoacyl-tRNA synthetase biochemistry. Limitations: This is tRNA-bound substrate discrimination, not evidence that serine supplements cause mistranslation. Evidence access: Primary abstract Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257
    Complete structured claim and evidence

  3. TARS2 interacted with inactive Rag complexes, especially GTP-bound RagC, and promoted RagA GTP loading.

    Human mitochondrial threonyl-tRNA synthetase / TARS2 → Human RagA GTP loading source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Cellular interaction and mTORC1 signaling experiments.
    limitations
    GTP-bound RagC here belongs to the inactive Rag configuration; GTP status has different implications for RagA and RagC.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    A threonine-processing protein also links nutrient availability to a growth-control switch.
    primary_references
    Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 98–104

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cellular interaction and mTORC1 signaling experiments. · source_derived_draft · unverified_draft

    ## l-threonine-tars2-rag A threonine-processing protein also links nutrient availability to a growth-control switch. TARS2 interacted with inactive Rag complexes, especially GTP-bound RagC, and promoted RagA GTP loading. Model: Cellular interaction and mTORC1 signaling experiments. Limitations: GTP-bound RagC here belongs to the inactive Rag configuration; GTP status has different implications for RagA and RagC. Evidence access: Primary abstract Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036
    Complete structured claim and evidence

  4. Disease-associated variants within TARS2 residues 301–381 reduced Rag binding in vitro; the associated mTORC1 mechanism was also investigated in zebrafish.

    Human mitochondrial threonyl-tRNA synthetase / TARS2 → Human TARS2 binding to Rag GTPases source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    18 newly reported individuals from 15 families, prior cases reviewed, in vitro assays and zebrafish modeling.
    limitations
    Likely mechanistic contribution, not proof that this pathway explains every patient feature.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    Some variants can affect signaling as well as the usual translation function.
    primary_references
    Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37454282/ · DOI 10.1016/j.gim.2023.100938
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 114–120

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 18 newly reported individuals from 15 families, prior cases reviewed, in vitro assays and zebrafish modeling. · source_derived_draft · unverified_draft

    ## l-threonine-tars2-rag-variants Some variants can affect signaling as well as the usual translation function. Disease-associated variants within TARS2 residues 301–381 reduced Rag binding in vitro; the associated mTORC1 mechanism was also investigated in zebrafish. Model: 18 newly reported individuals from 15 families, prior cases reviewed, in vitro assays and zebrafish modeling. Limitations: Likely mechanistic contribution, not proof that this pathway explains every patient feature. Evidence access: Primary abstract Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37454282/ · DOI 10.1016/j.gim.2023.100938
    Complete structured claim and evidence

  5. Cells lacking TARS2 failed to restore mTORC1 activation in response to threonine repletion; cytosolic TARS was not required for this signaling effect.

    Human mitochondrial threonyl-tRNA synthetase / TARS2 → Threonine-responsive human cellular mTORC1 activation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    TARS2 loss and threonine repletion in cultured cells.
    limitations
    This is a signaling endpoint, not a clinical threonine-repletion trial.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    Restoring the nutrient did not restore the signal when its machinery was missing.
    primary_references
    Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 106–112

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · TARS2 loss and threonine repletion in cultured cells. · source_derived_draft · unverified_draft

    ## l-threonine-tars2-repletion-failure Restoring the nutrient did not restore the signal when its machinery was missing. Cells lacking TARS2 failed to restore mTORC1 activation in response to threonine repletion; cytosolic TARS was not required for this signaling effect. Model: TARS2 loss and threonine repletion in cultured cells. Limitations: This is a signaling endpoint, not a clinical threonine-repletion trial. Evidence access: Primary abstract Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036
    Complete structured claim and evidence

  6. Seven newly reported TARS2 variants were linked to mitochondrial disease, with functional studies demonstrating impaired protein stability or function.

    Human mitochondrial threonyl-tRNA synthetase / TARS2 → Human TARS2 stability and catalytic function source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis.
    limitations
    Disease mechanisms differ by variant; response to threonine supplementation was not established.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    Enough amino acid cannot by itself guarantee a working loading enzyme.
    primary_references
    Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 82–88

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis. · source_derived_draft · unverified_draft

    ## l-threonine-tars2-variants Enough amino acid cannot by itself guarantee a working loading enzyme. Seven newly reported TARS2 variants were linked to mitochondrial disease, with functional studies demonstrating impaired protein stability or function. Model: Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis. Limitations: Disease mechanisms differ by variant; response to threonine supplementation was not established. Evidence access: Primary abstract Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257
    Complete structured claim and evidence

What acts on it

  1. GSNO treatment S-nitrosated human mitochondrial ThrRS and reduced both aminoacylation and editing activity in vitro.

    S-Nitrosoglutathione / GSNO → Human mitochondrial threonyl-tRNA synthetase / TARS2 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues.
    limitations
    GSNO is not reduced glutathione; this exposure does not predict effects of oral glutathione. H2O2 resistance and GSNO sensitivity were distinct in this study.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    Chemical modification of the enzyme can disrupt loading and proofreading.
    primary_references
    Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32484546/ · DOI 10.1093/nar/gkaa471
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 90–96

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues. · source_derived_draft · unverified_draft

    ## l-threonine-tars2-nitrosation Chemical modification of the enzyme can disrupt loading and proofreading. GSNO treatment S-nitrosated human mitochondrial ThrRS and reduced both aminoacylation and editing activity in vitro. Model: Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues. Limitations: GSNO is not reduced glutathione; this exposure does not predict effects of oral glutathione. H2O2 resistance and GSNO sensitivity were distinct in this study. Evidence access: Primary abstract Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32484546/ · DOI 10.1093/nar/gkaa471
    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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