Affinage

FDX1

Adrenodoxin, mitochondrial · UniProt P10109

Length
184 aa
Mass
19.4 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FDX1 is a mitochondrial [2Fe-2S] ferredoxin that serves as a specialized electron shuttle for multiple essential mitochondrial biosynthetic pathways, functionally distinct from its paralog FDX2. FDX1 donates electrons to mitochondrial cytochrome P450 enzymes for steroid hormone biosynthesis, to lipoyl synthase (LIAS) via direct binding to drive protein lipoylation required for TCA cycle function, and to COX15 for heme a synthesis during cytochrome c oxidase biogenesis; it also catalyzes reduction of ionophore-bound Cu(II) to Cu(I) for mitochondrial copper delivery (PMID:20547883, PMID:36280795, PMID:37453661, PMID:36848556, PMID:37858707). Deep mutational scanning identified acidic residues D136/D139 on alpha helix 3 as a critical protein–protein interaction surface essential for lipoylation and cuproptosis in cells, while dihydrolipoamide dehydrogenase (DLD) functions as an alternative FDX1 reductase (PMID:41423452). FDX1 expression is regulated transcriptionally by SF1/cJUN and NFKB1 and post-translationally by AKT1-mediated phosphorylation that inhibits its pro-oxidative and respiratory functions (PMID:28274746, PMID:40716652, PMID:39976173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Determination of the crystal structure of the bovine FDX1 ortholog established the architectural basis for redox partner recognition, revealing a [2Fe-2S] cluster at the domain interface and an asymmetric charged surface that mediates electrostatic steering toward reductase and P450 partners.

    Evidence X-ray crystallography at 1.85 Å resolution with MAD phasing of truncated bovine adrenodoxin

    PMID:9551550

    Open questions at the time
    • Structure was of a truncated construct; full-length human FDX1 structure not determined
    • Redox-state-dependent domain motion inferred but not captured in two states
  2. 2005 Medium

    Overexpression studies first linked FDX1 to mitochondrial ROS production and intrinsic apoptosis, demonstrating that excess FDX1 electron transfer disrupts mitochondrial membrane potential and triggers cytochrome c release independent of p53.

    Evidence Transient overexpression in 11 human cell lines with ROS, ΔΨm, cytochrome c release, and caspase activation measurements

    PMID:15927889

    Open questions at the time
    • Overexpression artifact not ruled out—endogenous role in apoptosis unconfirmed
    • No loss-of-function counterpart performed
  3. 2010 High

    Functional separation of the two human ferredoxins resolved a long-standing question: FDX1 is specifically required for mitochondrial P450-dependent steroidogenesis, whereas FDX2 supports Fe-S cluster and heme A biogenesis, and the two cannot efficiently substitute for each other.

    Evidence RNAi depletion in human cells with steroid conversion assays and Fe-S protein activity measurements

    PMID:20547883

    Open questions at the time
    • The molecular determinants of substrate specificity between FDX1 and FDX2 were not identified at this stage
    • Whether FDX1 had additional non-steroidogenic roles was unknown
  4. 2017 High

    NMR and calorimetry showed that FDX1 can bind the Fe-S assembly machinery (NFS1/ISD11/Acp) and support cluster assembly in vitro, but with lower affinity and rate than FDX2, explaining why FDX1 loss does not impair Fe-S biogenesis in cells.

    Evidence NMR interaction mapping, isothermal titration calorimetry, and reconstituted in vitro Fe-S assembly assays

    PMID:28001042

    Open questions at the time
    • Whether FDX1 ever contributes meaningfully to Fe-S assembly under physiological conditions remains unclear
  5. 2017 Medium

    Transcriptional regulation of FDX1 in steroidogenic cells was mapped, showing SF1 and cJUN cooperatively activate the Fdx1 promoter in Leydig cells, with SF1 being the essential factor.

    Evidence Promoter-reporter assays, ChIP, and RNAi in MA-10 and TM3 Leydig cells

    PMID:28274746

    Open questions at the time
    • Regulation in non-steroidogenic tissues not addressed
    • Whether SF1-dependent regulation is conserved in humans not shown
  6. 2020 Medium

    Cross-linking MS and NMR revealed that FDX1 binding to CYP24A1 allosterically remodels the P450 active site, establishing that FDX1 is not merely an electron donor but an allosteric regulator of P450 substrate binding and regioselectivity.

    Evidence Chemical cross-linking/MS and NMR of FDX1-CYP24A1 complex with functional assays

    PMID:32259445

    Open questions at the time
    • Generalizability to other mitochondrial P450s not tested
    • Structural detail of the allosteric conformational change limited
  7. 2022 High

    A major expansion of FDX1 function was established: FDX1 specifically provides electrons to lipoyl synthase (LIAS) for lipoyl cofactor biosynthesis, and domain-swap chimeras between FDX1 and FDX2 identified short sequence motifs that determine target specificity.

    Evidence CRISPR KO, in vitro electron transfer assays, chimeric ferredoxin domain-swap mutagenesis, lipoylation assays

    PMID:36280795

    Open questions at the time
    • Structural basis of FDX1-LIAS recognition not resolved at atomic level
    • Whether additional mitochondrial targets exist beyond steroidogenic P450s and LIAS was open
  8. 2023 High

    Multiple studies converged to show FDX1 directly binds LIAS and promotes its interaction with GCSH, that FDX1 loss abolishes lipoylation of four TCA cycle enzymes causing conditional lethality under normoxia, that FDX1 reduces ionophore-bound Cu(II) to deliver copper for cytochrome c oxidase metalation, and that FDX1 acts upstream of COX15 in heme a biosynthesis for CcO assembly.

    Evidence Co-IP/direct binding, CRISPR KO in human and rat cells, metabolite profiling, copper/heme measurements, COX15 genetic rescue, hypoxic rescue experiments

    PMID:36848556 PMID:37453661 PMID:37481209 PMID:37858707

    Open questions at the time
    • Whether FDX1 directly reduces COX15 or acts via an intermediary is not determined
    • The relative contribution of each pathway (lipoylation, heme a, copper delivery) to the lethal phenotype is not fully dissected
  9. 2023 Medium

    Epitranscriptomic regulation of FDX1 was identified: METTL16-mediated m6A modification of FDX1 mRNA, controlled by METTL16 lactylation (inhibited by SIRT2), increases FDX1 expression and cuproptosis sensitivity in gastric cancer.

    Evidence MeRIP, METTL16 lactylation site mapping, SIRT2 inhibition, cuproptosis assays in vitro/in vivo

    PMID:37863889

    Open questions at the time
    • Opposing result reported (METTL3/FMR1 decreases FDX1 in HCC); tissue- and m6A writer-specific effects not reconciled
    • Whether m6A regulation operates on FDX1 under normal physiology is unknown
  10. 2025 High

    Deep mutational scanning identified D136 and D139 on FDX1 alpha helix 3 as a critical protein–protein interaction interface essential for lipoylation and cuproptosis in cells, and discovered DLD as an alternative FDX1 reductase, expanding the FDX1 electron-supply network beyond FDXR.

    Evidence Systematic charge-reversal mutagenesis, cell-based lipoylation and cuproptosis assays, in vitro enzymatic assays

    PMID:41423452

    Open questions at the time
    • No co-crystal structure of FDX1 with LIAS or other partners via helix 3
    • Physiological relevance of DLD as FDX1 reductase versus FDXR not quantified in vivo
  11. 2025 High

    EPR spectroscopy provided direct spectroscopic evidence that FDX1 transfers electrons to elesclomol-Cu(II) both in vitro and in vivo, with higher affinity for this substrate than FDX2, establishing the biophysical basis for FDX1-specific copper reduction.

    Evidence EPR spectroscopy, molecular docking, low-temperature EPR in vitro and in cells

    PMID:40484707

    Open questions at the time
    • Whether FDX1 reduces physiological (non-elesclomol) copper complexes in mitochondria is not addressed
    • In vivo EPR was at low temperature, not under truly physiological conditions
  12. 2025 Medium

    Post-translational regulation of FDX1 was identified: AKT1 phosphorylates FDX1, inhibiting its function in cuproptosis and aerobic respiration while promoting glycolysis, with copper itself activating AKT signaling in a feedback loop.

    Evidence Phosphorylation assays, AKT1 inhibitor treatment, respiration and glycolysis measurements in triple-negative breast cancer cells

    PMID:39976173

    Open questions at the time
    • Phosphorylation site on FDX1 not mapped
    • Direct in vitro kinase assay not fully described
    • Whether this regulatory axis operates in non-cancer cells unknown
  13. 2025 Medium

    FDX1 overexpression was shown to trigger mitochondrial permeability transition pore opening, cytosolic release of mtDNA and mt-dsRNA, and activation of cGAS/STING and RIG-I/MDA5 innate immune pathways, linking FDX1 to type I interferon signaling independent of cuproptosis.

    Evidence FDX1 overexpression with mtDNA/dsRNA release assays, TBK1 phosphorylation, syngeneic orthotopic mouse models

    PMID:41199656

    Open questions at the time
    • Overexpression-driven; whether endogenous FDX1 levels activate this axis is unknown
    • Mechanism of mPTP opening by FDX1 not elucidated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the atomic-resolution structural basis of FDX1 partner selectivity via helix 3, whether FDX1 reduces physiological (non-ionophore) copper carriers, the relative in vivo contributions of FDXR versus DLD as FDX1 reductases, and whether FDX1's reported roles in innate immune activation and autophagy regulation reflect primary electron-transfer functions or indirect metabolic consequences.
  • No co-crystal structure of FDX1 with any physiological partner
  • No identified physiological mitochondrial copper complex reduced by FDX1
  • Relative pathway contributions to lethality not quantitatively dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0140104 molecular carrier activity 3
Localization
GO:0005739 mitochondrion 6
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-5357801 Programmed Cell Death 3
Partners
COX15CYP24A1DLDFDXRGCSHLIASNFS1

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Human FDX1 (adrenodoxin) is specifically required for cytochrome P450-dependent steroid hormone biosynthesis (e.g., cholesterol to pregnenolone, aldosterone, cortisol) in mitochondria, whereas the related FDX2 is essential for Fe/S cluster and heme A biosynthesis. RNAi depletion of FDX1 did not impair Fe/S protein biogenesis, while FDX2 depletion caused severe Fe/S protein defects and iron accumulation. FDX2 could not efficiently substitute for FDX1 in steroid conversion assays, demonstrating distinct substrate specificity. RNAi depletion in human cells, steroid conversion assays, Fe/S protein activity measurements, iron uptake assays Proceedings of the National Academy of Sciences of the United States of America High 20547883
2022 FDX1 (but not FDX2) is specifically required for lipoyl cofactor biosynthesis in addition to steroidogenesis and heme a synthesis. FDX1 provides electrons to lipoyl synthase (LIAS) to initiate the radical chain reaction. Swapping small conserved sequence motifs between FDX1 and FDX2 changed their respective target specificities, identifying these motifs as determinants of functional specificity. RNAi/CRISPR loss-of-function, in vitro electron transfer assays, chimeric ferredoxin domain-swap experiments, lipoylation assays Nature chemical biology High 36280795
2023 FDX1 directly binds lipoyl synthase (LIAS) and promotes LIAS functional interaction with the lipoyl carrier protein GCSH, thereby regulating cellular protein lipoylation. This function is independent of indirect regulation via Fe/S cluster biosynthesis. Loss of FDX1 results in loss of lipoylation of four TCA cycle enzymes, loss of cellular respiration, and conditional lethality under low glucose. Co-immunoprecipitation/direct binding assay, metabolite profiling, transcriptional profiling, siRNA knockdown, CRISPR KO The Journal of biological chemistry High 36778498 37453661
2023 FDX1 acts as a mitochondrial matrix reductase that catalyzes reduction of elesclomol-Cu(II) to Cu(I), releasing copper into the mitochondrial matrix where it metalates cytochrome c oxidase. FDX1 KO cells fail to rescue cytochrome c oxidase abundance/activity when treated with elesclomol in copper-deficient conditions, while copper delivery to non-mitochondrial cuproproteins is partially FDX1-independent. CRISPR KO, biochemical copper measurements, cytochrome c oxidase activity/abundance assays, genetic rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 36848556
1998 Crystal structure of truncated bovine adrenodoxin (Adx/FDX1 ortholog) Adx(4-108) at 1.85 Å resolution reveals a compact (α+β) fold with a large core domain and smaller interaction domain containing residues required for binding adrenodoxin reductase and cytochrome P450. The [2Fe-2S] cluster is located at the edge; charged residues form an asymmetric electric potential implicated in electrostatic steering of redox partner interactions. A domain motion linked to redox state change is suggested. X-ray crystallography (MAD phasing), electrostatic surface analysis Structure (London, England : 1993) High 9551550
2023 FDX1 is required for lipoylation under normoxia; under hypoxia (1% O2), FDX1 KO cells survive despite persistent loss of lipoylation, indicating that hypoxia rescues the lethality caused by lipoylation deficiency rather than restoring lipoylation via an alternative route. CRISPR KO, lipoylation western blot, hypoxic cell culture growth assays The Journal of biological chemistry High 37481209
2017 Both human FDX1 and FDX2 bind the cysteine desulfurase complex (NFS1/ISD11/Acp) via residues near the Fe-S cluster, and both can donate electrons to support Fe-S cluster assembly on ISCU in vitro, though FDX2 binds the complex more tightly and supports faster cluster assembly than FDX1. NMR spectroscopy (interaction mapping), isothermal titration calorimetry, in vitro Fe-S cluster assembly assays Biochemistry High 28001042
2023 FDX1 is essential for biogenesis of mitochondrial cytochrome c oxidase (CcO) in mammalian cells. FDX1 KO rat cardiomyocytes show reduced CcO abundance and assembly, decreased copper and heme a/a3 levels. Overexpression of COX15 (heme a synthase) partially rescues COX1 abundance, placing FDX1 upstream of COX15 in heme a biosynthesis and CcO assembly. CRISPR-Cas9 KO, mitochondrial respiration assays, BN-PAGE CcO assembly analysis, copper measurement, heme a measurement, genetic rescue (COX15 overexpression) Journal of molecular biology High 37858707
2025 Deep mutational scanning identified two conserved solvent-exposed acidic residues on FDX1 alpha helix 3 (D136 and D139) as essential for both cuproptosis induction and lipoylation in cells, despite retaining enzymatic activity in vitro, indicating helix 3 is a critical protein-protein interaction interface. Additionally, dihydrolipoamide dehydrogenase (DLD) was identified as an alternative FDX1 reductase both in vitro and in cells. Deep mutational scanning, charge-reversal mutagenesis, cell-based cuproptosis and lipoylation assays, in vitro enzymatic assays, structural analysis Nature communications High 41423452
2025 EPR spectroscopy demonstrated direct electron transfer from reduced FDX1 to the elesclomol-Cu(II) complex both in vitro and in vivo. FDX1 has higher binding affinity for elesclomol-Cu(II) than its homolog FDX2, explaining the functional specificity. Elesclomol-Cu(II) is a more efficient electron acceptor from FDX1 than free Cu(II). Electron paramagnetic resonance (EPR) spectroscopy, molecular docking, low-temperature EPR measurements in vitro and in vivo Chemistry (Weinheim an der Bergstrasse, Germany) High 40484707
2025 AKT1 phosphorylates FDX1, and this phosphorylation inhibits FDX1-induced cuproptosis and aerobic respiration while promoting glycolysis in triple-negative breast cancer cells. Copper activates AKT signaling which then suppresses FDX1 function. Phosphorylation assays, AKT1 inhibitor treatment, in vitro and in vivo functional assays, glycolysis and respiration measurements Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39976173
2020 Allosteric coupling exists between substrate binding and adrenodoxin (FDX1/Adx) recognition in CYP24A1. Chemical cross-linking/MS and NMR revealed that Adx binding induces a conformational change in CYP24A1 F and G helices required for substrate binding. A semiconserved nonpolar interface contact may influence CYP24A1 regioselectivity. Chemical cross-linking coupled to mass spectrometry, NMR spectroscopy, CYP24A1 functional assays Biochemistry Medium 32259445
2017 Transcription factors SF1 and cJUN cooperate to activate the Fdx1 promoter in Leydig cells. SF1 is recruited to regulatory elements between -124 and -306 bp of the Fdx1 promoter. RNAi demonstrated SF1 is required for Fdx1 transcriptional regulation, while cJUN cooperates with SF1 but is not individually essential. Promoter-reporter assays, chromatin immunoprecipitation, RNA interference, transfection in MA-10 and TM3 Leydig cells The Journal of steroid biochemistry and molecular biology Medium 28274746
2005 Overexpression of adrenodoxin (FDX1/Adx) in human cells induces ROS production in mitochondria, disrupts mitochondrial transmembrane potential, causes cytochrome c release, and activates caspases leading to apoptosis in a p53-independent manner. Transient overexpression, ROS measurement, mitochondrial membrane potential assay (ΔΨ), cytochrome c release assay, caspase activation assay, cell viability assays across 11 cell lines Biological chemistry Medium 15927889
2023 FDX1 interacts with G6PD and reduces its protein stability, leading to decreased NADPH and GSH levels, which enhances copper-induced cell death (cuproptosis) in endometriosis cells. Co-immunoprecipitation, protein stability assays, NADPH/GSH measurement, cell death assays, mouse model Apoptosis : an international journal on programmed cell death Low 37119432
2025 p53 enhances FDX1-mediated cuproptosis in hepatocellular carcinoma via ferredoxin reductase (FDXR); p53 activation increases FDXR expression, which promotes FDX1 upregulation, leading to DLAT oligomerization and cuproptosis. FDXR knockdown reverses p53-mediated sensitization, placing FDXR between p53 and FDX1 in the cuproptosis pathway. p53 overexpression/knockdown, siRNA-mediated FDXR knockdown, DLAT oligomerization assays (western blot, immunofluorescence), cell viability assays, xenograft mouse model Frontiers in oncology Medium 40630211
2025 PUMA directly binds FDX1 at its R155 site and promotes DLAT/DLST oligomerization and reduction of LIAS expression, activating cuproptosis. PUMA binding also increases FDX1 ubiquitination at K182, leading to FDX1 degradation. Co-immunoprecipitation, immunofluorescence, dual-luciferase assays, RNA immunoprecipitation, ubiquitination assays, xenograft mouse model Cellular oncology (Dordrecht, Netherlands) Medium 41212484
2025 FDX1 overexpression triggers mitochondrial permeability transition pore opening, leading to cytosolic release of mitochondrial DNA and double-stranded RNA. These DAMPs activate cGAS and RIG-I/MDA5 sensors, triggering TBK1 phosphorylation and type I interferon response that reshapes the tumor microenvironment in ccRCC, linking FDX1 to innate immune activation independent of cuproptosis. FDX1 overexpression, mtDNA/mt-dsRNA cytosolic release assays, cGAS/RIG-I pathway activation assays (TBK1 phosphorylation), orthotopic syngeneic mouse models, flow cytometry Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 41199656
2025 FDX1 coordinates autophagic activity in ovarian cancer by modulating the AMPK and mTOR signaling pathways and preserving mitochondrial integrity/DLAT-DLST sulfation to maintain autophagic flux; FDX1 is predominantly localized to cytoplasm and mitochondria. FDX1 knockdown/overexpression, AMPK/mTOR pathway analysis, autophagic flux assays, mitochondrial integrity assays, in vivo xenograft NPJ precision oncology Low 40629130
2025 METTL3-mediated m6A modification of FDX1 mRNA reduces FDX1 protein expression via the m6A reader FMR1, which inhibits FDX1 translation, thereby conferring resistance to cuproptosis in hepatocellular carcinoma. m6A-MeRIP, METTL3/FMR1 knockdown, FDX1 protein expression assays, cuproptosis sensitivity assays, xenograft models Communications biology Medium 41501140
2023 METTL16 lactylation at K229 (inhibited by SIRT2) promotes m6A modification on FDX1 mRNA, increasing FDX1 expression and thereby promoting cuproptosis in gastric cancer cells. m6A modification assays (MeRIP), METTL16 lactylation site mapping, SIRT2 inhibition, cuproptosis assays in vitro and in vivo Nature communications Medium 37863889
2025 FDX1 promotes elesclomol-induced PANoptosis in DLBCL by increasing IRF3 phosphorylation, which activates IFN-β-dependent signaling. FDX1 overexpression sensitizes DLBCL cells to elesclomol-Cu cell death both in vitro and in patient-derived xenografts. FDX1 overexpression/knockdown, IRF3 phosphorylation assays, IFN-β signaling assays, PDX models, patient cohort correlation analysis Oncogene Medium 40240522
2025 FDX1 directly binds FMR1 protein and upregulates its expression in ccRCC, which subsequently restrains Bcl-2 and N-cadherin while enhancing Cleaved Caspase-3 and E-cadherin expression; FMR1 knockdown reverses the anti-tumor effect of FDX1 overexpression. Co-IP assays, TMT proteomic sequencing, RNA-sequencing, orthotopic mouse models, FMR1 knockdown rescue assays Cell death discovery Low 40118855
2025 FDX1 regulates HIF-1α protein levels under severe hypoxia in glioblastoma cells, and FDX1 knockdown reduces hypoxia-induced phosphorylation/activation of ATM, DNA-PKcs, Akt, and EGFR, thereby sensitizing cells to radiation. HIF-1α does not reciprocally regulate FDX1, placing FDX1 upstream of HIF-1α in this pathway. siRNA knockdown, phosphorylation western blotting, radiation sensitivity assays, HIF-1α protein measurement under hypoxia International journal of molecular sciences Low 40244269
2025 The lncRNA PVT1 directly binds to the FDX1 promoter at the -104/-41 bp region, increases H3K27ac deposition, and recruits transcription factor SF1 to activate FDX1 transcription, thereby promoting cuproptosis in colorectal cancer. ChIRP (chromatin isolation by RNA purification), ChIP, luciferase reporter assays, molecular docking, xenograft model Redox biology Medium 40505346
2025 NFKB1 directly binds the FDX1 promoter to transcriptionally upregulate FDX1 in glioblastoma cells, as validated by dual-luciferase assay. NFKB1 knockdown reduces FDX1 expression, and FDX1 overexpression partially rescues the anti-tumor effect of NFKB1 knockdown, placing NFKB1 upstream of FDX1. Dual-luciferase promoter assay, NFKB1 knockdown, FDX1 overexpression rescue, in vivo intracranial xenograft Biochemical pharmacology Medium 40716652
2023 miR-21-5p directly binds the 3'-UTR of FDX1 mRNA to mediate its degradation in clear cell renal cell carcinoma, as validated by luciferase reporter assay. miR-21-5p inhibition suppresses ccRCC cell growth and invasion in a manner compensated by FDX1 knockdown. 3'-UTR luciferase reporter assay, miR-21-5p mimic/inhibitor, FDX1 knockdown rescue, cell growth/invasion assays Cells Medium 36611966

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Assembly of iron-sulfur clusters. Identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. The Journal of biological chemistry 566 9582371
2023 Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer. Nature communications 362 37863889
2010 Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 318 20547883
1999 Functional assignment of the ORF2-iscS-iscU-iscA-hscB-hscA-fdx-ORF3 gene cluster involved in the assembly of Fe-S clusters in Escherichia coli. Journal of biochemistry 228 10544286
1999 Hyperproduction of recombinant ferredoxins in escherichia coli by coexpression of the ORF1-ORF2-iscS-iscU-iscA-hscB-hs cA-fdx-ORF3 gene cluster. Journal of biochemistry 173 10393315
2023 FDX1 regulates cellular protein lipoylation through direct binding to LIAS. The Journal of biological chemistry 152 37453661
1998 New aspects of electron transfer revealed by the crystal structure of a truncated bovine adrenodoxin, Adx(4-108). Structure (London, England : 1993) 133 9551550
2022 Functional spectrum and specificity of mitochondrial ferredoxins FDX1 and FDX2. Nature chemical biology 123 36280795
2017 Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis. Biochemistry 116 28001042
2023 FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery. Proceedings of the National Academy of Sciences of the United States of America 102 36848556
2024 FDX1 downregulation activates mitophagy and the PI3K/AKT signaling pathway to promote hepatocellular carcinoma progression by inducing ROS production. Redox biology 92 39128228
2001 Crystal structure of Escherichia coli Fdx, an adrenodoxin-type ferredoxin involved in the assembly of iron-sulfur clusters. Biochemistry 72 11551196
2002 Cellular surface display of dimeric Adx and whole cell P450-mediated steroid synthesis on E. coli. Journal of biotechnology 67 12007866
2022 Cuproptosis-Related MiR-21-5p/FDX1 Axis in Clear Cell Renal Cell Carcinoma and Its Potential Impact on Tumor Microenvironment. Cells 66 36611966
1995 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat. Endocrinology 54 7895695
2010 Glutamatergic fine tuning with ADX-10059: a novel therapeutic approach for migraine? Expert opinion on investigational drugs 50 20218930
1993 The fdx gene encoding the [2Fe--2S] ferredoxin of Halobacterium salinarium (H. halobium). Molecular & general genetics : MGG 49 8510664
2023 FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis. Apoptosis : an international journal on programmed cell death 48 37119432
2022 Cuproptosis-Related Gene - SLC31A1, FDX1 and ATP7B - Polymorphisms are Associated with Risk of Lung Cancer. Pharmacogenomics and personalized medicine 48 35923305
1997 Molecular characterization of Fdx1, a putidaredoxin-type [2Fe-2S] ferredoxin able to transfer electrons to the dioxin dioxygenase of Sphingomonas sp. RW1. European journal of biochemistry 47 9288905
2022 Multi-omics pan-cancer study of cuproptosis core gene FDX1 and its role in kidney renal clear cell carcinoma. Frontiers in immunology 46 36605188
2012 Separate FeS scaffold and carrier functions for SufB₂C₂ and SufA during in vitro maturation of [2Fe2S] Fdx. Journal of inorganic biochemistry 41 23018275
2023 LINC02362/hsa-miR-18a-5p/FDX1 axis suppresses proliferation and drives cuproptosis and oxaliplatin sensitivity of hepatocellular carcinoma. American journal of cancer research 39 38058825
1987 Na-dependent effects of DOCA on cellular transport properties of CCDs from ADX rabbits. The American journal of physiology 37 3661724
2025 AKT1 Phosphorylates FDX1 to Promote Cuproptosis Resistance in Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 35 39976173
2021 The role of FDX1 in granulosa cell of Polycystic ovary syndrome (PCOS). BMC endocrine disorders 31 34130686
2023 METTL3 promotes non-small-cell lung cancer growth and metastasis by inhibiting FDX1 through copper death-associated pri-miR-21-5p maturation. Epigenomics 30 38126112
1996 Dexamethasone Does Not Prevent Seven-Day ADX-Induced Apoptosis in the Dentate Gyrus of the Rat Hippocampus. Stress (Amsterdam, Netherlands) 30 9807061
2023 Lipoylation is dependent on the ferredoxin FDX1 and dispensable under hypoxia in human cells. The Journal of biological chemistry 29 37481209
2023 FDX1 inhibits thyroid cancer malignant progression by inducing cuprotosis. Heliyon 29 37554785
2023 FDX1 Is Required for the Biogenesis of Mitochondrial Cytochrome c Oxidase in Mammalian Cells. Journal of molecular biology 29 37858707
2012 Chlamydomonas reinhardtii chloroplasts contain a homodimeric pyruvate:ferredoxin oxidoreductase that functions with FDX1. Plant physiology 26 23154536
2024 Upregulation of miR-3130-5p Enhances Hepatocellular Carcinoma Growth by Suppressing Ferredoxin 1 : miR-3130-5p Enhances HCC Growth via Inhibiting FDX1. Current molecular pharmacology 25 40103455
2005 Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria. Biological chemistry 25 15927889
2023 Adrenomedullin/FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 37698353
2011 Functional characterization of Fdx1: evidence for an evolutionary relationship between P450-type and ISC-type ferredoxins. Journal of molecular biology 24 21945528
2017 ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in cognitive flexibility induced by withdrawal from 'binge-like' ethanol exposure in rats. Behavioural brain research 23 29030082
2024 Cuproptosis-Related Gene FDX1 Suppresses the Growth and Progression of Colorectal Cancer by Retarding EMT Progress. Biochemical genetics 21 38520567
2023 FDX1 regulates leydig cell ferroptosis mediates PM2.5-induced testicular dysfunction of mice. Ecotoxicology and environmental safety 19 37517308
2024 Elabela alleviates cuproptosis and vascular calcification in vitaminD3- overloaded mice via regulation of the PPAR-γ /FDX1 signaling. Molecular medicine (Cambridge, Mass.) 18 39567863
2023 The FDX1 methylation regulatory mechanism in the malignant phenotype of glioma. Genomics 17 36889365
2017 Transcription factors SF1 and cJUN cooperate to activate the Fdx1 promoter in MA-10 Leydig cells. The Journal of steroid biochemistry and molecular biology 17 28274746
2015 Association between CCDC132, FDX1 and TNFSF13 gene polymorphisms and the risk of IgA nephropathy. Nephrology (Carlton, Vic.) 17 26370181
2015 Crystal structure and biochemical characterization of Chlamydomonas FDX2 reveal two residues that, when mutated, partially confer FDX2 the redox potential and catalytic properties of FDX1. Photosynthesis research 17 26526668
2018 Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish. Journal of neuroendocrinology 16 29486070
2011 Differential effect of the mGlu5 receptor positive allosteric modulator ADX-47273 on early and late hippocampal LTP. Neuropharmacology 15 21640734
2024 Curcuminoid PBPD induces cuproptosis and endoplasmic reticulum stress in cervical cancer via the Notch1/RBP-J/NRF2/FDX1 pathway. Molecular carcinogenesis 14 38801356
2023 A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint. International journal of molecular sciences 14 37298135
2020 Evidence of Allosteric Coupling between Substrate Binding and Adx Recognition in the Vitamin D Carbon-24 Hydroxylase CYP24A1. Biochemistry 14 32259445
2019 A comparison of EGFR mutation status in tissue and plasma cell-free DNA detected by ADx-ARMS in advanced lung adenocarcinoma patients. Translational lung cancer research 14 31106124
1995 Comparison between GC-MS and the EMIT II, Abbott ADx, and Roche OnLine immunoassays for the determination of THCCOOH. Journal of analytical toxicology 14 7500617
2025 Copper-mediated SEC14L3 promotes cuproptosis to inhibit hepatocellular carcinoma growth via ERK/YY1/FDX1 axis. Communications biology 13 40274982
2024 Liraglutide Improves PCOS Symptoms in Rats by Targeting FDX1. Reproductive sciences (Thousand Oaks, Calif.) 13 38441776
2012 Comparative screening of K-ras mutations in colorectal cancer and lung cancer patients using a novel real-time PCR with ADx-K-ras kit and Sanger DNA sequencing. Cell biochemistry and biophysics 13 22048888
2024 FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma. World journal of gastrointestinal surgery 11 38983344
2023 FDX1 regulates cellular protein lipoylation through direct binding to LIAS. bioRxiv : the preprint server for biology 11 36778498
2003 Xenorhabdus nematophila requires an intact iscRSUA-hscBA-fdx operon to colonize Steinernema carpocapsae nematodes. Journal of bacteriology 11 12775707
2022 A mitochondrial ADXR-ADX-P450 electron transport chain is essential for maternal gametophytic control of embryogenesis in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 10 35046016
2025 LncRNA PVT1 promotes cuproptosis through transcriptional activation of FDX1 in colorectal cancer. Redox biology 9 40505346
2024 The Role of Cuproptosis Key Factor FDX1 in Gastric Cancer. Current pharmaceutical biotechnology 9 38918976
2025 FDX1 promotes elesclomol-induced PANoptosis in diffuse large B-cell lymphoma via activating IRF3/IFN-β signaling. Oncogene 8 40240522
2025 Metabolome-wide association identifies ferredoxin-1 (FDX1) as a determinant of cholesterol metabolism and cardiovascular risk in Asian populations. Nature cardiovascular research 8 40360795
2025 Engineered RAP-anchored copper-escorting liposomes for FDX1-targeted cuproptosis in glioblastoma therapy‌. Theranostics 8 40756352
2022 Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury. Biomolecules 7 35327585
1991 Evaluation of the Abbott ADx Amphetamine/Methamphetamine II abused drug assay: comparison to TDx, EMIT, and GC/MS methods. Journal of analytical toxicology 7 1779660
2025 Targeting FDX1 by trilobatin to inhibit cuproptosis in doxorubicin-induced cardiotoxicity. British journal of pharmacology 6 39933533
2025 FDX1 facilitates elesclomol-induced cuproptosis and promotes glioblastoma development via transcription factor NFKB1. Biochemical pharmacology 6 40716652
2024 Cuproptosis-Related Gene FDX1 Identified as a Potential Target for Human Ovarian Aging. Reproductive sciences (Thousand Oaks, Calif.) 6 38689081
2024 The study on cuproptosis in Alzheimer's disease based on the cuproptosis key gene FDX1. Frontiers in aging neuroscience 6 39759399
2025 Electron Paramagnetic Resonance Insights into Direct Electron Transfer Between FDX1 and Elesclomol-Cu2+ Complex in Cuproptosis. Chemistry (Weinheim an der Bergstrasse, Germany) 5 40484707
2023 Confirmation of the predictive function of cuproptosis-related gene FDX1 in clear cell renal carcinoma using qRT-PCR and western blotting. Aging 5 37432054
2025 Anti-FDX1 Autoantibody as a Potential Biomarker for Non-Small Cell Lung Cancer Detection. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 4 39699293
2025 p53 enhances elesclomol-Cu-induced cuproptosis in hepatocellular carcinoma via FDXR-mediated FDX1 upregulation. Frontiers in oncology 4 40630211
2025 Copper ionophore complex ES-Cu synergizes with quercetin to target FDX1, promote cuproptosis, and reverse lenvatinib resistance in hepatocellular carcinoma cells. Journal of advanced research 4 40902896
2025 FDX1 overexpression inhibits the growth and metastasis of clear cell renal cell carcinoma by upregulating FMR1 expression. Cell death discovery 3 40118855
2025 FDX1 Regulates the Phosphorylation of ATM, DNA-PKcs Akt, and EGFR and Affects Radioresistance Under Severe Hypoxia in the Glioblastoma Cell Line T98G. International journal of molecular sciences 3 40244269
2025 Polystyrene nanoplastics carrying copper ion induce FDX1-mediated cuproptosis. Ecotoxicology and environmental safety 3 40850113
2025 Copper Chelation by Penicillamine Protects Against Doxorubicin-Induced Cardiomyopathy by Suppressing FDX1-Mediated Cuproptosis. Biomolecules 3 41008627
2023 Effect of the mGlu4 positive allosteric modulator ADX-88178 on parkinsonism, psychosis-like behaviours and dyskinesia in the MPTP-lesioned marmoset. Psychopharmacology 3 37516708
2025 Modulation of Cuproptosis Pathway Genes (DLAT, FDX1) and Antioxidant Enzyme Activities in Obese Mice in Response to Quercetin and Calorie Restriction. DNA and cell biology 2 40354319
2025 Tanshinone IIA promotes METTL3/METTL14-mediated FDX1 m6A modification to induce cuproptosis in bladder cancer. Toxicology research 2 40843273
2025 Cuproptosis-Related Gene FDX1 Induces Malignant Progression and Immune Suppression in Triple-Negative Breast Cancer. Biochemical genetics 2 40911146
2025 Targeting FDX1 with Icaritin attenuates neuronal cuproptosis by reconciling mitochondrial fission-fusion dynamics and bioenergetic homeostasis. Free radical biology & medicine 2 40998065
2025 Fe-S Protein FDX1 Triggers Tumor-Intrinsic Innate Immunity via Mitochondrial Nucleic Acids Release to Orchestrate Ferroptosis in CCRCC. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41199656
2025 Unraveling the miR-144-3p/PUMA pathway: a novel regulator of FDX1-mediated cuproptosis in colorectal cancer. Cellular oncology (Dordrecht, Netherlands) 2 41212484
2024 C1-FDX is required for the assembly of mitochondrial complex I and subcomplexes of complex V in Arabidopsis. PLoS genetics 2 39356718
2026 Precision targeting of FDX1-mediated cuproptosis by a ROS-responsive hydrogel for myocardial ischemia-reperfusion injury treatment. Theranostics 1 41355968
2026 METTL3-mediated m6A modification of FDX1 confers resistance to cuproptosis and promotes hepatocellular carcinoma progression. Communications biology 1 41501140
2026 Client distribution between Chlamydomonas FDX1 and FDX2 in carbon, nitrogen and sulfur assimilation. bioRxiv : the preprint server for biology 1 41648530
2025 Mycobacterium tuberculosis stimulates cuproptosis by regulating Lnc-Gm5532 to target FDX1 for bacteria intracellular survival. International immunopharmacology 1 40449270
2025 Modulating ovarian cancer progression through FDX1-driven autophagy. NPJ precision oncology 1 40629130
2025 [Acupuncture inhibits cuproptosis to prolong the time window of thrombolysis by down-regulating cerebral FDX1 and DLAT in rats with cerebral infarction]. Zhen ci yan jiu = Acupuncture research 1 40691025
2025 METTL14 promotes hippocampal neuronal cuproptosis via m6A modification on FDX1 mRNA in cerebral ischemia-reperfusion injury. Brain research bulletin 1 40769372
2025 Marine Natural Product Chagosendine C Induces Cuproptosis in Colorectal Cancer Cells by Targeting FDX1. Journal of the American Chemical Society 1 40977283
2025 Integrated Multi-omics and Experimental Validation Reveal FDX1/LIAS-Mediated Cuproptosis as a Potential Driver of Diabetic Kidney Disease. Biological trace element research 1 41100003
2025 Deep Mutational Scanning of FDX1 Identifies Key Structural Determinants of Lipoylation and Cuproptosis. Nature communications 1 41423452
2025 Targeting cuproptosis by FDX1 in acetaminophen-induced liver injury. Chemico-biological interactions 0 40987411
2025 Mitochondrial uncoupling sensitizes gastric cancer cells to elesclomol-induced cuproptosis via FDX1/DLAT upregulation. Free radical biology & medicine 0 41407052
2025 Role of Ferredoxin 1 (FDX1) in cancer and its therapeutic potential. Cancer pathogenesis and therapy 0 41853121
2024 Knocking Down LncRNA-GAS5 Restores the Inhibition of Cuprotosis Protein FDX-1 by Acinetobacter baumannii. Polish journal of microbiology 0 39670641