Affinage

FDX1

Adrenodoxin, mitochondrial · UniProt P10109

Length
184 aa
Mass
19.4 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FDX1 (adrenodoxin/ferredoxin 1) is a mitochondrial [2Fe-2S] ferredoxin that acts as an electron shuttle dedicated to a defined set of biosynthetic and metabolic reactions, functionally distinct from its homolog FDX2, which carries out Fe/S cluster and heme A biosynthesis (PMID:20547883, PMID:36280795). Its founding role is to donate electrons to mitochondrial cytochrome P450 enzymes to drive steroidogenesis (e.g., CYP11A1) and vitamin D metabolism (CYP24A1), where Adx binding allosterically remodels the P450 active site to enable substrate binding and tune regioselectivity (PMID:20547883, PMID:32259445). A second, central role is in mitochondrial protein lipoylation: FDX1 directly binds lipoyl synthase (LIAS), supplies the reducing equivalents that initiate its radical-SAM chemistry, and promotes LIAS engagement with the lipoyl carrier GCSH, thereby lipoylating all four lipoylation-dependent TCA cycle enzymes; loss of FDX1 abolishes respiration and is conditionally lethal under low glucose, a defect rescued for growth but not lipoylation by hypoxia (PMID:36280795, PMID:37453661, PMID:36778498, PMID:37481209). FDX1 is also required upstream of COX15 for cytochrome c oxidase biogenesis, controlling CcO assembly, copper, and heme a/a3 content (PMID:37858707). As a matrix reductase, FDX1 reduces the elesclomol-Cu(II) complex to Cu(I) to release bioavailable copper for CcO metalation, and excess copper handling through this activity drives cuproptosis via accumulation of lipoylated protein aggregates (PMID:36848556, PMID:40484707). The acidic solvent-exposed residues D136 and D139 on alpha-helix 3 form the critical protein-protein interface required for both lipoylation and cuproptosis, independent of intrinsic electron-transfer activity (PMID:41423452). FDX1 activity is constrained by AKT1-mediated phosphorylation, which suppresses cuproptosis and respiration in favor of glycolysis (PMID:39976173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Established the structural basis for how the ferredoxin engages its electron-acceptor partners, revealing a redox-coupled domain motion and an asymmetric charge surface that electrostatically steers interactions with adrenodoxin reductase and P450.

    Evidence X-ray crystallography of truncated bovine adrenodoxin at 1.85 Å with functional domain annotation

    PMID:9551550

    Open questions at the time
    • Resolved an ortholog fragment rather than full-length human FDX1
    • Did not address the lipoylation or copper-reductase interfaces later defined on alpha-helix 3
  2. 2010 High

    Resolved the long-standing ambiguity between the two human ferredoxins, demonstrating FDX1 is specifically required for steroidogenic P450 electron donation and not for Fe/S cluster or heme A biosynthesis, which belong to FDX2.

    Evidence RNAi depletion of FDX1 vs FDX2 in human cells with orthogonal readouts for steroidogenesis, heme A, and Fe/S maturation

    PMID:20547883

    Open questions at the time
    • Did not yet identify lipoylation or copper roles for FDX1
    • Mechanism of substrate discrimination between FDX1 and FDX2 not defined
  3. 2017 High

    Tested whether FDX1 can participate in Fe/S assembly biochemically, showing both ferredoxins bind the NFS1/ISD11/ACP desulfurase and can support in vitro cluster assembly, but FDX2 binds tighter and is faster — clarifying the in vivo division of labor.

    Evidence NMR interface mapping, ITC, and in vitro Fe/S cluster assembly on ISCU

    PMID:28001042

    Open questions at the time
    • In vitro competence does not establish in vivo Fe/S role for FDX1
    • Structural determinants of differential affinity not defined
  4. 2020 Medium

    Defined the mechanism of FDX1-P450 functional coupling, showing adrenodoxin binding allosterically reorganizes the CYP24A1 F/G helices to permit substrate binding and influence regioselectivity.

    Evidence Chemical cross-linking mass spectrometry, NMR perturbation, and CYP24A1 functional assays

    PMID:32259445

    Open questions at the time
    • Single P450 partner examined
    • Allosteric model not extended to other mitochondrial P450s
  5. 2022 High

    Assigned FDX1 a third biosynthetic role in lipoyl cofactor synthesis and pinpointed the sequence motifs that distinguish FDX1 from FDX2 substrate specificity.

    Evidence Cell-based KO and motif-swap mutants, in vitro reconstitution of the lipoyl synthase radical reaction, and structural analysis

    PMID:36280795

    Open questions at the time
    • Did not resolve the physical FDX1–LIAS interface at residue level
    • Did not separate lipoylation from Fe/S epistatically
  6. 2023 High

    Demonstrated FDX1 directly binds LIAS to promote its interaction with GCSH and drive lipoylation independent of Fe/S biosynthesis, with loss abolishing respiration and causing conditional lethality.

    Evidence Co-IP/pulldown, metabolite and transcriptional profiling, and CRISPR/RNAi loss-of-function with metabolic phenotyping

    PMID:36778498 PMID:37453661

    Open questions at the time
    • Stoichiometry and structure of the FDX1–LIAS–GCSH assembly unresolved
    • Reductant source for the reaction not defined in this study
  7. 2023 High

    Tested whether an alternative lipoate route exists under hypoxia, showing hypoxia rescues FDX1-KO growth but not lipoylation, confirming FDX1/LIAS as the sole biosynthetic path.

    Evidence CRISPR KO of FDX1 or LIAS, growth at normoxia vs 1% O2, and direct lipoylation measurement

    PMID:37481209

    Open questions at the time
    • Mechanism by which hypoxia bypasses the growth requirement not fully defined
  8. 2023 High

    Identified FDX1 as the matrix reductase that converts elesclomol-Cu(II) to bioavailable Cu(I) for cytochrome c oxidase metalation, distinguishing mitochondrial from non-mitochondrial copper delivery.

    Evidence FDX1 KO with elesclomol-copper treatment, CcO activity and abundance assays, and copper quantification

    PMID:36848556

    Open questions at the time
    • FDX1-independent copper delivery routes to non-mitochondrial cuproproteins not molecularly defined
  9. 2023 High

    Placed FDX1 within the CcO biogenesis pathway upstream of heme a synthase COX15, showing copper supplementation cannot rescue but COX15 overexpression partially restores COX1.

    Evidence CRISPR KO in rat cardiomyocytes with CcO assembly, copper, and heme a measurements plus COX15 rescue

    PMID:37858707

    Open questions at the time
    • Direct mechanism linking FDX1 to heme a synthesis not defined
    • Whether FDX1 acts via lipoylation or independently in this context unclear
  10. 2023 Medium

    Began connecting FDX1 to upstream regulation and tumor cell death by linking epitranscriptomic (METTL16 m6A) and proteostatic control to FDX1 expression and cuproptosis sensitivity.

    Evidence m6A-seq/MeRIP, METTL16 lactylation site mapping, and cuproptosis assays in gastric cancer

    PMID:37863889

    Open questions at the time
    • Single cancer context
    • Direct effect of m6A on FDX1 protein output vs mRNA stability not fully separated
  11. 2025 High

    Used unbiased mutational scanning to define the essential functional interface, showing D136/D139 on alpha-helix 3 are required for both lipoylation and cuproptosis despite preserved electron-transfer activity, and identified DLD as an alternative FDX1 reductase.

    Evidence Deep mutational scanning, site-directed mutagenesis, in vitro enzymatic assays, and cell-based cuproptosis/lipoylation readouts

    PMID:41423452

    Open questions at the time
    • Structural detail of how D136/D139 engages partners not solved
    • Relative in vivo contributions of DLD vs canonical reductase unquantified
  12. 2025 High

    Provided direct spectroscopic confirmation of FDX1-driven electron transfer to elesclomol-Cu and explained FDX1's specificity over FDX2 by higher binding affinity for the ES-Cu complex.

    Evidence Low-temperature/power-saturation EPR, molecular docking, and in vitro/in vivo electron-transfer assays

    PMID:40484707

    Open questions at the time
    • Behavior toward free copper vs chelated copper in physiological settings not fully resolved
  13. 2025 Medium

    Revealed post-translational and protein-level regulation of FDX1 activity through AKT1 phosphorylation that toggles cells from FDX1-dependent respiration/cuproptosis toward glycolysis.

    Evidence Kinase-substrate assays, AKT1 gain/loss-of-function, metabolic and cuproptosis readouts, and AKT inhibitor + ionophore rescue in vivo

    PMID:39976173

    Open questions at the time
    • Phosphosite(s) on FDX1 not explicitly mapped in abstract
    • Single lab; mechanism of how phosphorylation impairs electron transfer unclear
  14. 2025 Medium

    Extended the regulatory network with transcriptional, partner-binding, and immunogenic consequences of FDX1, including PVT1/SF1-driven transcription, FDXR/p53-mediated upregulation, PUMA binding, and induction of an mtDNA/dsRNA-driven interferon response.

    Evidence ChIRP/ChIP, Co-IP, dual-luciferase, fractionation for cytosolic mtDNA/dsRNA, and in vivo tumor models across multiple cancers

    PMID:40505346 PMID:40630211 PMID:41199656 PMID:41212484

    Open questions at the time
    • Most interactions rest on single Co-IP/single-lab evidence
    • Direct vs indirect nature of several partner interactions not reciprocally validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FDX1's three biochemical activities (P450 electron donation, lipoylation, copper reduction) are partitioned, regulated, and prioritized within a single mitochondrion remains unresolved.
  • No high-resolution structure of full-length human FDX1 bound to LIAS or to the copper complex
  • Physiological reductant choice (canonical reductase vs DLD) under different metabolic states unclear
  • Whether cuproptosis is a physiological program or a pharmacological liability not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0140104 molecular carrier activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
CYP11A1CYP24A1FMR1G6PDGCSHLIASNFS1PUMA

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Human FDX1 (adrenodoxin/ferredoxin 1) is specifically required for steroidogenesis via electron donation to mitochondrial cytochrome P450 enzymes (e.g., CYP11A1 converting cholesterol to pregnenolone), but is NOT required for Fe/S cluster or heme A biosynthesis in human cells; that role belongs exclusively to FDX2. RNAi-mediated depletion of FDX1 or FDX2 in human cells; functional assays for steroid conversion, heme A synthesis, and Fe/S protein maturation Proceedings of the National Academy of Sciences of the United States of America High 20547883
2022 FDX1 is specifically required for steroidogenesis, heme a biosynthesis, and lipoyl cofactor biosynthesis. In the lipoylation pathway FDX1 provides electrons to kickstart the radical chain reaction catalyzed by lipoyl synthase (LIAS). Target specificity of FDX1 versus FDX2 was assigned to small conserved sequence motifs; swapping these motifs exchanged their substrate specificities. Cell-based functional assays with FDX1/FDX2 KO or swapped motif mutants; in vitro reconstitution of lipoyl synthase radical reaction; structural analysis Nature chemical biology High 36280795
2023 FDX1 directly binds the lipoyl synthase enzyme LIAS, promoting LIAS's functional interaction with the lipoyl carrier protein GCSH and thereby driving mitochondrial protein lipoylation; this regulation is independent of Fe/S cluster biosynthesis. Loss of FDX1 impairs all four lipoylation-dependent TCA cycle enzymes, abolishes cellular respiration, and is conditionally lethal under low glucose. Co-immunoprecipitation/pulldown (direct FDX1–LIAS binding); metabolite profiling; transcriptional profiling; CRISPR/RNAi loss-of-function with defined metabolic phenotypes The Journal of biological chemistry High 36778498 37453661
2023 FDX1 is dispensable under 1% O2 in cultured human cells. FDX1 is essential for lipoic acid cofactor production via the ISC-containing enzyme lipoyl synthase; hypoxia rescues the growth defect of FDX1 KO cells but does not rescue lipoylation, arguing against an alternative biosynthetic route for lipoate under hypoxia. CRISPR KO of FDX1 or lipoyl synthase; growth assays at normoxia vs. 1% O2; biochemical measurement of lipoylation The Journal of biological chemistry High 37481209
2023 FDX1 acts as the mitochondrial matrix reductase that catalyzes reduction of ES-Cu(II) to Cu(I), releasing copper inside mitochondria where it is bioavailable for metalation of cytochrome c oxidase. In FDX1-null cells, ES fails to rescue CcO abundance/activity under copper deficiency, while ES-mediated copper delivery to non-mitochondrial cuproproteins continues via FDX1-independent mechanisms. Genetic KO of FDX1 combined with elesclomol-copper treatment; biochemical measurement of CcO activity and abundance; copper quantification; cell-biological assays Proceedings of the National Academy of Sciences of the United States of America High 36848556
2023 FDX1 is required for the biogenesis of cytochrome c oxidase (CcO) in mammalian cardiomyocytes; FDX1 KO reduces CcO abundance, assembly, copper levels, and heme a/a3 levels. Copper supplementation does not rescue CcO, but overexpression of heme a synthase (COX15) partially rescues COX1 abundance, placing FDX1 upstream of COX15 in CcO biogenesis. CRISPR-Cas9 KO in rat cardiomyocyte cell line; measurement of CcO complex assembly, copper, and heme a; rescue experiments with COX15 overexpression Journal of molecular biology High 37858707
1998 Crystal structure of truncated bovine adrenodoxin (Adx/FDX1 ortholog) Adx(4-108) determined at 1.85 Å resolution. The protein has a core domain and an interaction domain (35 residues) containing all residues involved in binding adrenodoxin reductase (AR) and cytochrome P450. A domain motion coupled to the redox state of the [2Fe-2S] cluster was identified, and a strikingly asymmetric charge distribution implicated in electrostatic steering of AR and P450 interactions. X-ray crystallography at 1.85 Å (MAD phasing using Fe atoms); functional validation from prior biochemical studies Structure (London, England : 1993) High 9551550
2017 Both human FDX1 and FDX2 bind the cysteine desulfurase complex (NFS1/ISD11/ACP) with residues near the Fe/S cluster involved in interaction; FDX2 binds more tightly than FDX1. Both reduced ferredoxins become oxidized in the presence of the complex + L-cysteine, and both can support in vitro Fe/S cluster assembly on ISCU, though FDX2 is faster. NMR spectroscopy (binding interface mapping); isothermal titration calorimetry; in vitro Fe/S cluster assembly assay Biochemistry High 28001042
2025 Deep mutational scanning of FDX1 identified two conserved solvent-exposed residues on alpha helix 3, D136 and D139, as essential for both cuproptosis induction and protein lipoylation in cells; charge-reversal mutations abolish both activities despite retaining full in vitro enzymatic (electron transfer) activity. Dihydrolipoamide dehydrogenase (DLD, the E3 subunit) was identified as an alternative FDX1 reductase both in cells and in vitro. Deep mutational scanning; site-directed mutagenesis; cell-based cuproptosis and lipoylation assays; in vitro enzymatic assays; structural and genomic analyses Nature communications High 41423452
2025 AKT1 phosphorylates FDX1, abrogating FDX1-induced cuproptosis and aerobic respiration while promoting glycolysis in triple-negative breast cancer cells. Copper activates AKT signaling, which in turn inhibits FDX1 via phosphorylation. Kinase-substrate phosphorylation assays; AKT1 overexpression/knockdown; cell-based cuproptosis and metabolic readouts; in vitro and in vivo rescue experiments with AKT1 inhibitors + copper ionophores Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39976173
2025 PUMA directly binds FDX1 at its R155 site, enhancing FDX1 function and promoting DLAT/DLST oligomerization and cuproptosis. PUMA binding also raises ubiquitination at FDX1 K182, leading to FDX1 degradation during cuproptosis. Co-IP; immunofluorescence; dual-luciferase reporter assay (for upstream miR-144-3p/PUMA axis); Western blot for DLAT oligomerization and FDX1 ubiquitination Cellular oncology (Dordrecht, Netherlands) Medium 41212484
2025 EPR spectroscopy provided direct spectroscopic evidence that reduced FDX1 transfers electrons to the ES-Cu2+ complex in vitro and in cells; ES-Cu2+ accepts electrons from FDX1 more readily than free Cu2+. EPR and molecular docking showed FDX1 has higher binding affinity for ES-Cu2+ than its homolog FDX2, explaining functional specificity. Low-temperature and power saturation EPR spectroscopy; molecular docking; in vitro and in vivo electron transfer assays Chemistry (Weinheim an der Bergstrasse, Germany) High 40484707
2020 Substrate binding and adrenodoxin (Adx/FDX1) recognition in CYP24A1 are allosterically coupled: Adx binding induces conformational changes in the F and G helices of CYP24A1 that are required for substrate binding, as shown by differential chemical cross-linking and NMR perturbations. A semiconserved nonpolar interaction at the CYP24A1–Adx interface influences CYP24A1 regioselectivity. Chemical cross-linking coupled to mass spectrometry; NMR spectroscopy; CYP24A1 functional assays Biochemistry Medium 32259445
2005 Overexpression of adrenodoxin (Adx/FDX1) in human cell lines causes ROS production in mitochondria, disruption of mitochondrial transmembrane potential, cytochrome c release, and caspase activation, leading to apoptosis independent of p53. Transient overexpression; ROS assays; mitochondrial membrane potential measurement; cytochrome c release assay; caspase activation assay; cell viability across 11 cell lines Biological chemistry Medium 15927889
2017 Transcription factors SF1 and cJUN cooperate to activate the mouse Fdx1 promoter in Leydig cells. SF1 is recruited to a region between -124 and -306 bp of the Fdx1 promoter and is required (by RNA interference) for Fdx1 transcription, while cJUN is dispensable but cooperates with SF1 to upregulate expression. Luciferase reporter assays; chromatin immunoprecipitation (ChIP); RNA interference; promoter deletion analysis in MA-10 and TM3 Leydig cells The Journal of steroid biochemistry and molecular biology Medium 28274746
2023 METTL16 lactylation at K229 (inhibited by SIRT2) promotes m6A modification on FDX1 mRNA, increasing FDX1 expression and sensitizing gastric cancer cells to cuproptosis. Copper stress promotes METTL16 lactylation, linking metabolic state to FDX1-dependent cell death. m6A-seq/MeRIP; METTL16 lactylation site mapping; SIRT2 inhibition (AGK2); cell-based cuproptosis assays in vitro and in vivo Nature communications Medium 37863889
2025 p53 enhances elesclomol-Cu-induced cuproptosis in HCC via FDXR-mediated FDX1 upregulation: p53 activation increases FDXR expression, which promotes FDX1 upregulation and subsequent DLAT oligomerization; FDXR knockdown reverses p53-mediated sensitization to cuproptosis. p53 overexpression/knockdown; siRNA-mediated FDXR/FDX1 knockdown; Western blot for DLAT oligomerization; cell viability assay; in vivo xenograft Frontiers in oncology Medium 40630211
2023 FDX1 interacts with G6PD and reduces G6PD protein stability, decreasing NADPH and GSH levels and thereby enhancing cuproptosis in endometriosis cells. Co-immunoprecipitation (FDX1–G6PD interaction); G6PD stability assays; NADPH/GSH measurement; cell-based cuproptosis assays; mouse ectopic endometrial tissue model Apoptosis : an international journal on programmed cell death Low 37119432
2025 FDX1 overexpression triggers mitochondrial permeability transition pore opening, leading to cytosolic release of mitochondrial DNA and mt-dsRNA, activating cGAS and RIG-I/MDA5 sensors, TBK1 phosphorylation, and a type I interferon response that precedes ferroptosis and reshapes the tumor microenvironment. FDX1 overexpression; mitochondrial permeability transition assays; cytosolic fractionation for mtDNA/mt-dsRNA; cGAS/RIG-I pathway activation assays; orthotopic syngeneic models Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 41199656
2025 FDX1 bound directly to FMR1 protein and upregulated FMR1 expression, subsequently restraining Bcl-2 and N-cadherin while enhancing ALCAM, cleaved caspase-3, and E-cadherin; FMR1 knockdown reversed FDX1-mediated suppression of ccRCC growth and metastasis. Co-IP; TMT proteomic sequencing; RNA sequencing; cell phenotype and in vivo mouse orthotopic tumor experiments Cell death discovery Low 40118855
2025 PVT1 lncRNA directly binds the FDX1 promoter (35/98 nt of PVT1 binding -104/-41 bp region), increases H3K27ac deposition, and activates FDX1 transcription; PVT1 also recruits SF1 to the FDX1 promoter, further enhancing FDX1 expression and cuproptosis in colorectal cancer. ChIRP; ChIP; luciferase reporter assay; bioinformatics; molecular docking; xenograft model Redox biology Medium 40505346
2025 Trilobatin (TLB) directly binds FDX1 (confirmed by surface plasmon resonance) and suppresses FDX1-mediated cuproptosis after doxorubicin treatment, reducing mitochondrial oxidative stress and cuproptosis-related proteins in a dose-dependent manner. Surface plasmon resonance binding assay; molecular dynamics simulation; siRNA knockdown of FDX1; in vivo and in vitro cardiotoxicity models; Western blot for cuproptosis markers British journal of pharmacology Medium 39933533
2025 Icaritin (ICT) directly binds FDX1 with high affinity (confirmed by surface plasmon resonance and molecular dynamics simulation), downregulates FDX1 protein expression, and inhibits FDX1-mediated cuproptosis in hippocampal neurons, reducing DLAT oligomerization and restoring copper homeostasis. Surface plasmon resonance; computational molecular docking and trajectory simulations; FDX1 knockdown; Western blot for DLAT and lipoylation markers; mitochondrial functional assays Free radical biology & medicine Medium 40998065

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 400 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 321 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 163 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 130 36280795
2017 Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis. Biochemistry 117 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 114 36848556
2024 FDX1 downregulation activates mitophagy and the PI3K/AKT signaling pathway to promote hepatocellular carcinoma progression by inducing ROS production. Redox biology 102 39128228
2001 Crystal structure of Escherichia coli Fdx, an adrenodoxin-type ferredoxin involved in the assembly of iron-sulfur clusters. Biochemistry 72 11551196
2022 Cuproptosis-Related MiR-21-5p/FDX1 Axis in Clear Cell Renal Cell Carcinoma and Its Potential Impact on Tumor Microenvironment. Cells 70 36611966
2002 Cellular surface display of dimeric Adx and whole cell P450-mediated steroid synthesis on E. coli. Journal of biotechnology 68 12007866
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
2023 FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis. Apoptosis : an international journal on programmed cell death 52 37119432
2022 Cuproptosis-Related Gene - SLC31A1, FDX1 and ATP7B - Polymorphisms are Associated with Risk of Lung Cancer. Pharmacogenomics and personalized medicine 50 35923305
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
2022 Multi-omics pan-cancer study of cuproptosis core gene FDX1 and its role in kidney renal clear cell carcinoma. Frontiers in immunology 47 36605188
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
2025 AKT1 Phosphorylates FDX1 to Promote Cuproptosis Resistance in Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 44 39976173
2023 LINC02362/hsa-miR-18a-5p/FDX1 axis suppresses proliferation and drives cuproptosis and oxaliplatin sensitivity of hepatocellular carcinoma. American journal of cancer research 42 38058825
2012 Separate FeS scaffold and carrier functions for SufB₂C₂ and SufA during in vitro maturation of [2Fe2S] Fdx. Journal of inorganic biochemistry 42 23018275
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 41 40103455
1987 Na-dependent effects of DOCA on cellular transport properties of CCDs from ADX rabbits. The American journal of physiology 37 3661724
2023 METTL3 promotes non-small-cell lung cancer growth and metastasis by inhibiting FDX1 through copper death-associated pri-miR-21-5p maturation. Epigenomics 31 38126112
2021 The role of FDX1 in granulosa cell of Polycystic ovary syndrome (PCOS). BMC endocrine disorders 31 34130686
2023 Lipoylation is dependent on the ferredoxin FDX1 and dispensable under hypoxia in human cells. The Journal of biological chemistry 30 37481209
2023 FDX1 Is Required for the Biogenesis of Mitochondrial Cytochrome c Oxidase in Mammalian Cells. Journal of molecular biology 30 37858707
1996 Dexamethasone Does Not Prevent Seven-Day ADX-Induced Apoptosis in the Dentate Gyrus of the Rat Hippocampus. Stress (Amsterdam, Netherlands) 30 9807061
2023 FDX1 inhibits thyroid cancer malignant progression by inducing cuprotosis. Heliyon 29 37554785
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 27 37698353
2012 Chlamydomonas reinhardtii chloroplasts contain a homodimeric pyruvate:ferredoxin oxidoreductase that functions with FDX1. Plant physiology 26 23154536
2005 Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria. Biological chemistry 25 15927889
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 22 38520567
2024 Elabela alleviates cuproptosis and vascular calcification in vitaminD3- overloaded mice via regulation of the PPAR-γ /FDX1 signaling. Molecular medicine (Cambridge, Mass.) 20 39567863
2023 The FDX1 methylation regulatory mechanism in the malignant phenotype of glioma. Genomics 19 36889365
2023 FDX1 regulates leydig cell ferroptosis mediates PM2.5-induced testicular dysfunction of mice. Ecotoxicology and environmental safety 19 37517308
2024 Curcuminoid PBPD induces cuproptosis and endoplasmic reticulum stress in cervical cancer via the Notch1/RBP-J/NRF2/FDX1 pathway. Molecular carcinogenesis 17 38801356
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
2025 LncRNA PVT1 promotes cuproptosis through transcriptional activation of FDX1 in colorectal cancer. Redox biology 14 40505346
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
2023 FDX1 regulates cellular protein lipoylation through direct binding to LIAS. bioRxiv : the preprint server for biology 13 36778498
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
2025 Targeting FDX1 by trilobatin to inhibit cuproptosis in doxorubicin-induced cardiotoxicity. British journal of pharmacology 11 39933533
2025 Engineered RAP-anchored copper-escorting liposomes for FDX1-targeted cuproptosis in glioblastoma therapy‌. Theranostics 11 40756352
2024 FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma. World journal of gastrointestinal surgery 11 38983344
2003 Xenorhabdus nematophila requires an intact iscRSUA-hscBA-fdx operon to colonize Steinernema carpocapsae nematodes. Journal of bacteriology 11 12775707
2025 Metabolome-wide association identifies ferredoxin-1 (FDX1) as a determinant of cholesterol metabolism and cardiovascular risk in Asian populations. Nature cardiovascular research 10 40360795
2024 The study on cuproptosis in Alzheimer's disease based on the cuproptosis key gene FDX1. Frontiers in aging neuroscience 10 39759399
2025 FDX1 promotes elesclomol-induced PANoptosis in diffuse large B-cell lymphoma via activating IRF3/IFN-β signaling. Oncogene 9 40240522
2024 The Role of Cuproptosis Key Factor FDX1 in Gastric Cancer. Current pharmaceutical biotechnology 9 38918976
2025 FDX1 facilitates elesclomol-induced cuproptosis and promotes glioblastoma development via transcription factor NFKB1. Biochemical pharmacology 8 40716652
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 8 40902896
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 p53 enhances elesclomol-Cu-induced cuproptosis in hepatocellular carcinoma via FDXR-mediated FDX1 upregulation. Frontiers in oncology 6 40630211
2025 Marine Natural Product Chagosendine C Induces Cuproptosis in Colorectal Cancer Cells by Targeting FDX1. Journal of the American Chemical Society 6 40977283
2024 Cuproptosis-Related Gene FDX1 Identified as a Potential Target for Human Ovarian Aging. Reproductive sciences (Thousand Oaks, Calif.) 6 38689081
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 5 39699293
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
2025 Copper Chelation by Penicillamine Protects Against Doxorubicin-Induced Cardiomyopathy by Suppressing FDX1-Mediated Cuproptosis. Biomolecules 5 41008627
2025 Deep Mutational Scanning of FDX1 Identifies Key Structural Determinants of Lipoylation and Cuproptosis. Nature communications 5 41423452
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
2026 Precision targeting of FDX1-mediated cuproptosis by a ROS-responsive hydrogel for myocardial ischemia-reperfusion injury treatment. Theranostics 4 41355968
2025 FDX1 overexpression inhibits the growth and metastasis of clear cell renal cell carcinoma by upregulating FMR1 expression. Cell death discovery 4 40118855
2025 Tanshinone IIA promotes METTL3/METTL14-mediated FDX1 m6A modification to induce cuproptosis in bladder cancer. Toxicology research 4 40843273
2025 Polystyrene nanoplastics carrying copper ion induce FDX1-mediated cuproptosis. Ecotoxicology and environmental safety 4 40850113
2025 Targeting FDX1 with Icaritin attenuates neuronal cuproptosis by reconciling mitochondrial fission-fusion dynamics and bioenergetic homeostasis. Free radical biology & medicine 4 40998065
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 Unraveling the miR-144-3p/PUMA pathway: a novel regulator of FDX1-mediated cuproptosis in colorectal cancer. Cellular oncology (Dordrecht, Netherlands) 3 41212484
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
2026 METTL3-mediated m6A modification of FDX1 confers resistance to cuproptosis and promotes hepatocellular carcinoma progression. Communications biology 2 41501140
2026 FDX1-mediated cuproptosis promotes cholestatic liver injury exacerbated by taurocholic acid-enhanced copper accumulation. Cell death discovery 2 41513631
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 [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 2 40691025
2025 Cuproptosis-Related Gene FDX1 Induces Malignant Progression and Immune Suppression in Triple-Negative Breast Cancer. Biochemical genetics 2 40911146
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 Mitochondrial uncoupling sensitizes gastric cancer cells to elesclomol-induced cuproptosis via FDX1/DLAT upregulation. Free radical biology & medicine 2 41407052
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 METTL14 promotes hippocampal neuronal cuproptosis via m6A modification on FDX1 mRNA in cerebral ischemia-reperfusion injury. Brain research bulletin 1 40769372
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 Mettl1 mitigates sepsis-induced cardiomyopathy via inhibition of FDX1-dependent cuproptosis. Gene 1 41232822
2025 Atractylenolide III mitigates polycystic ovary syndrome by activating FDX1-mediated proliferation of ovarian granulocyte cells via PI3K/AKT/mTOR. Journal of ovarian research 1 41469708
2026 PRR15 suppresses renal cell carcinoma progression via the NF-κB/FDX1 axis to induce cuproptosis and mitochondrial dysfunction. Oncogene 0 41673093
2025 Targeting cuproptosis by FDX1 in acetaminophen-induced liver injury. Chemico-biological interactions 0 40987411

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