Component

Human NFU1 iron-sulfur cluster carrier

Human NFU1 iron-sulfur cluster carrier. Species, exposure and limitations are retained in 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 it acts on

  1. The NFU1 C-domain guides cluster transfer along increasing interaction affinity from ISCA1 toward LIAS.

    Human NFU1 iron-sulfur cluster carrier → Lipoic acid synthetase / LIAS source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"}
    experimental_model
    Recombinant protein interaction and cluster-insertion analysis
    exposure
    NFU1-ISCA1 donor complex
    limitations
    Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human proteins
    plain_language
    Protein-to-protein recognition helps deliver the cluster to the correct destination.
    primary_references
    [ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
    tissue_or_cell_type
    LIAS radical-SAM site

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 377–388

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein interaction and cluster-insertion analysis · source_derived_draft · unverified_draft

    ### ala-nfu1-affinity-gradient The NFU1 C-domain guides cluster transfer along increasing interaction affinity from ISCA1 toward LIAS. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protein-to-protein recognition helps deliver the cluster to the correct destination. organism: Human proteins tissue_or_cell_type: LIAS radical-SAM site experimental_model: Recombinant protein interaction and cluster-insertion analysis limitations: Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site. exposure: NFU1-ISCA1 donor complex evidence_span: {"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"} [ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
    Complete structured claim and evidence

  2. NFU1 forms a tight complex with LIAS and efficiently restores its auxiliary cluster during turnover in vitro.

    Human NFU1 iron-sulfur cluster carrier → LIAS auxiliary [4Fe-4S] site source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
    experimental_model
    Purified human LIAS turnover and cluster-transfer assays
    exposure
    LIAS with candidate iron-sulfur cluster donors
    limitations
    Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human recombinant proteins
    plain_language
    NFU1 replenishes the sulfur-supplying cluster.
    primary_references
    [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
    tissue_or_cell_type
    Mitochondrial lipoyl synthesis machinery

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 325–336

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft

    ### ala-nfu1-aux-repair NFU1 forms a tight complex with LIAS and efficiently restores its auxiliary cluster during turnover in vitro. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: NFU1 replenishes the sulfur-supplying cluster. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
    Complete structured claim and evidence

  3. The reported NFU1 splice-disrupting variant eliminated detectable mature mitochondrial NFU1 and accompanied lipoate-synthesis and 2-oxoacid dehydrogenase defects.

    Human NFU1 iron-sulfur cluster carrier → Mitochondrial protein lipoylation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"}
    experimental_model
    Two families with Fe-S disorders and fibroblast gene complementation
    exposure
    NFU1 and BOLA3 pathogenic variants; isoform-specific rescue
    limitations
    Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human
    plain_language
    The cofactor pathway depends on correctly assembled iron-sulfur machinery.
    primary_references
    [ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011
    tissue_or_cell_type
    Fibroblasts and mitochondrial enzymes
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 507–518

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two families with Fe-S disorders and fibroblast gene complementation · source_derived_draft · unverified_draft

    ### ala-nfu1-patient-defect The reported NFU1 splice-disrupting variant eliminated detectable mature mitochondrial NFU1 and accompanied lipoate-synthesis and 2-oxoacid dehydrogenase defects. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor pathway depends on correctly assembled iron-sulfur machinery. organism: Human tissue_or_cell_type: Fibroblasts and mitochondrial enzymes experimental_model: Two families with Fe-S disorders and fibroblast gene complementation limitations: Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction. exposure: NFU1 and BOLA3 pathogenic variants; isoform-specific rescue evidence_span: {"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"} [ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. BOLA3 did not directly enhance Fe-S cluster transfer from NFU1 or GLRX5 to LIAS in the purified assay.

    Human BOLA3 → LIAS catalytic turnover source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
    experimental_model
    Purified human LIAS turnover and cluster-transfer assays
    exposure
    LIAS with candidate iron-sulfur cluster donors
    limitations
    Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human recombinant proteins
    plain_language
    A protein can be essential in cells without stimulating this isolated transfer step.
    primary_references
    [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
    tissue_or_cell_type
    Mitochondrial lipoyl synthesis machinery

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 338–349

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft

    ### ala-bola3-direct-assay-null BOLA3 did not directly enhance Fe-S cluster transfer from NFU1 or GLRX5 to LIAS in the purified assay. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A protein can be essential in cells without stimulating this isolated transfer step. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
    Complete structured claim and evidence

  2. An NFU1-ISCA1 heterodimer delivers a [4Fe-4S] cluster to the radical-SAM site of LIAS.

    Human NFU1-ISCA1 complex → LIAS radical-SAM [4Fe-4S] site source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"}
    experimental_model
    Recombinant protein interaction and cluster-insertion analysis
    exposure
    NFU1-ISCA1 donor complex
    limitations
    Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human proteins
    plain_language
    A separate assembly route equips the radical-generating site.
    primary_references
    [ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
    tissue_or_cell_type
    LIAS radical-SAM site

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 364–375

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein interaction and cluster-insertion analysis · source_derived_draft · unverified_draft

    ### ala-nfu1-isca1-radical-site An NFU1-ISCA1 heterodimer delivers a [4Fe-4S] cluster to the radical-SAM site of LIAS. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate assembly route equips the radical-generating site. organism: Human proteins tissue_or_cell_type: LIAS radical-SAM site experimental_model: Recombinant protein interaction and cluster-insertion analysis limitations: Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site. exposure: NFU1-ISCA1 donor complex evidence_span: {"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"} [ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
    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