FDXR

Summary

Gene Symbol: FDXR
Description: ferredoxin reductase
Alias: ADXR, ANOA, NADPH:adrenodoxin oxidoreductase, mitochondrial, adrenodoxin reductase, adrenodoxin-NADP(+) reductase, ferredoxin--NADP(+) reductase
Species: human
Products:     FDXR

Top Publications

  1. Druck T, Cheung D, Park D, Trapasso F, Pichiorri F, Gaspari M, et al. Fhit-Fdxr interaction in the mitochondria: modulation of reactive oxygen species generation and apoptosis in cancer cells. Cell Death Dis. 2019;10:147 pubmed publisher
  2. Efimova V, Isaeva L, Rubtsov M, Novikova L. Analysis of In Vivo Activity of the Bovine Cholesterol Hydroxylase/Lyase System Proteins Expressed in Escherichia coli. Mol Biotechnol. 2019;61:261-273 pubmed publisher
    ..of the mammalian adrenal cortex cells, consists of cytochrome P450scc (CYP11A1), adrenodoxin (Adx), and adrenodoxin reductase (AdR) and performs the first stage of the steroidogenesis: AdR and Adx enable the electron transfer ..
  3. Raavi V, Surendran J, Karthik K, Paul S, Thayalan K, Arunakaran J, et al. Measurement of γ-H2AX foci, miRNA-101, and gene expression as a means to quantify radiation-absorbed dose in cancer patients who had undergone radiotherapy. Radiat Environ Biophys. 2019;58:69-80 pubmed publisher
    ..In this study, we have measured the absorbed dose using γ-H2AX, gene (GADD45A, FDXR, and CDKN1A) and miRNA-101 expression in blood samples of cancer patients (n = 20) who had undergone partial-..
  4. Lacombe J, Sima C, Amundson S, Zenhausern F. Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review. PLoS ONE. 2018;13:e0198851 pubmed publisher
    ..Twenty-seven genes showed a significant Spearman's correlation with radiation dose. Individually, TNFSF4, FDXR, MYC, ZMAT3 and GADD45A provided the best discrimination of radiation dose < 2 Gy and dose ≥ 2 Gy according to ..
  5. Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park H. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci U S A. 2011;108:10139-43 pubmed publisher
    ..to all steroid hormones, pregnenolone, is synthesized from cholesterol by an enzyme complex comprising adrenodoxin reductase (AdR), adrenodoxin (Adx), and a cytochrome P450 (P450scc or CYP11A1)...
  6. Lam V, Raineki C, Wang L, Chiu M, Lee G, Ellis L, et al. Role of corticosterone in anxiety- and depressive-like behavior and HPA regulation following prenatal alcohol exposure. Prog Neuropsychopharmacol Biol Psychiatry. 2019;90:1-15 pubmed publisher
    ..in mediating effects of stress in both adult females and males following PAE, adrenalectomy with CORT replacement (ADXR) was utilized to produce similar CORT levels among prenatal treatment groups before exposure to chronic ..
  7. Agbenyegah S, Abend M, Atkinson M, Combs S, Trott K, Port M, et al. Impact of Inter-Individual Variance in the Expression of a Radiation-Responsive Gene Panel Used for Triage. Radiat Res. 2018;190:226-235 pubmed publisher
    ..eight candidate genes ( DAGLA, WNT3, CD177, PLA2G16, WLS, POU2AF1, STAT4 and PRF1), we examined two more genes ( FDXR and DDB2) widely used in ex vivo whole blood experiments...
  8. Slone J, Peng Y, Chamberlin A, Harris B, Kaylor J, McDonald M, et al. Biallelic mutations in FDXR cause neurodegeneration associated with inflammation. J Hum Genet. 2018;63:1211-1222 pubmed publisher
    ..Recently, we have identified biallelic mutations in the mitochondrial flavoprotein "ferredoxin reductase" (FDXR) gene as a novel cause of mitochondriopathy, peripheral neuropathy, and optic atrophy...
  9. Kharechkina E, Nikiforova A, Kruglov A. Pyridine nucleotides regulate the superoxide anion flash upon permeabilization of mitochondrial membranes: An MCLA-based study. Free Radic Biol Med. 2018;124:473-483 pubmed publisher
    ..indicate that, in conditions close to pathophysiological, matrix NADPH oxidoreductase(s), presumably, an adrenodoxin reductase in complex with adrenodoxin, can essentially contribute to SA flashes associated with transient or ..

More Information

Publications54

  1. Muhsain S, Lang M, Abu Bakar A. Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress. Toxicol Appl Pharmacol. 2015;282:77-89 pubmed publisher
    ..The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation...
  2. Schiffer L, Anderko S, Hobler A, Hannemann F, Kagawa N, Bernhardt R. A recombinant CYP11B1 dependent Escherichia coli biocatalyst for selective cortisol production and optimization towards a preparative scale. Microb Cell Fact. 2015;14:25 pubmed publisher
    ..hydroxylation requires reducing equivalents which are provided from NADPH via a redox chain, consisting of adrenodoxin reductase (AdR) and adrenodoxin (Adx)...
  3. Lee Y, Pujol Canadell M, Shuryak I, Perrier J, Taveras M, Patel P, et al. Candidate protein markers for radiation biodosimetry in the hematopoietically humanized mouse model. Sci Rep. 2018;8:13557 pubmed publisher
    ..Forty-six proteins were differentially expressed in response to radiation exposure. FDXR, BAX, DDB2 and ACTN1 proteins were shown to have dose-dependent response with a fold change greater than 2...
  4. Keam S, Gulati T, Gamell C, Caramia F, Arnau G, Huang C, et al. Biodosimetric transcriptional and proteomic changes are conserved in irradiated human tissue. Radiat Environ Biophys. 2018;57:241-249 pubmed publisher
    ..To do this, we evaluated the quantitative changes of a set of dosimetric transcripts consisting of FDXR, BAX, BCL2, CDKN1A, DDB2, BBC3, GADD45A, GDF15, MDM2, SERPINE1, TNFRSF10B, PLK3, SESN2 and VWCE in guided pre- and ..
  5. Brzóska K, Kruszewski M. Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose. Radiat Environ Biophys. 2015;54:353-63 pubmed publisher
    ..6, and 2 Gy. The mRNA level of 16 genes (ATF3, BAX, BBC3, BCL2, CDKN1A, DDB2, FDXR, GADD45A, GDF15, MDM2, PLK3, SERPINE1, SESN2, TNFRSF10B, TNFSF4, and VWCE) was assessed by reverse transcription ..
  6. Bajpai P, Srinivasan S, Ghosh J, Nagy L, Wei S, Guengerich F, et al. Targeting of splice variants of human cytochrome P450 2C8 (CYP2C8) to mitochondria and their role in arachidonic acid metabolism and respiratory dysfunction. J Biol Chem. 2014;289:29614-30 pubmed publisher
    ..acids and 20-hydroxyeicosatetraenoic acid when reconstituted with adrenodoxin and adrenodoxin reductase. HepG2 cells stably expressing variant 3 generated higher levels of reactive oxygen species and showed a ..
  7. Ehrhardt M, Gerber A, Zapp J, Hannemann F, Bernhardt R. Human CYP27A1 catalyzes hydroxylation of β-sitosterol and ergosterol. Biol Chem. 2016;397:513-8 pubmed publisher
    ..by in vitro experiments applying purified human CYP27A1 and its redox partners adrenodoxin (Adx) and adrenodoxin reductase (AdR)...
  8. Abdulmughni A, Jóźwik I, Putkaradze N, Brill E, Zapp J, Thunnissen A, et al. Characterization of cytochrome P450 CYP109E1 from Bacillus megaterium as a novel vitamin D3 hydroxylase. J Biotechnol. 2017;243:38-47 pubmed publisher
    ..In an in vitro system using bovine adrenodoxin reductase (AdR) and adrenodoxin (Adx4-108), VD3 was converted by CYP109E1 into several ..
  9. Soltani B, Ghaemi N, Sadeghizadeh M, Najafi F. Redox maintenance and concerted modulation of gene expression and signaling pathways by a nanoformulation of curcumin protects peripheral blood mononuclear cells against gamma radiation. Chem Biol Interact. 2016;257:81-93 pubmed publisher
    ..response genes in irradiated PBMC revealed a similar profile for DNA damage response and repair genes including FDXR, XPC, DDB2, and GADD45 in DNC-treated cells compared to IR control...
  10. Saberi A, Khodamoradi E, Tahmasebi Birgani M, Makvandi M. Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats. Asian Pac J Cancer Prev. 2015;16:8553-7 pubmed
    ..Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-..
  11. Okumura H, Uchikado Y, Omoto I, Motomura M, Kita Y, Sasaki K, et al. Ferredoxin Reductase Is Useful for Predicting the Effect of Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma. Anticancer Res. 2015;35:6471-4 pubmed
    Ferredoxin reductase (Fdxr) is the mitochondrial cytochrome P-450 NADPH reductase. Fdxr overexpression increases the sensitivity of tumor cells to apoptosis in response to chemotherapy through reactive oxygen species (ROS) production...
  12. Milczarek R, Sokołowska E, Rybakowska I, Kaletha K, Klimek J. Paraquat inhibits progesterone synthesis in human placental mitochondria. Placenta. 2016;43:41-6 pubmed publisher
    ..However PQ has not inhibited combined activity of adrenodoxin reductase and adrenodoxin...
  13. O Brien G, Cruz Garcia L, Majewski M, Grepl J, Abend M, Port M, et al. FDXR is a biomarker of radiation exposure in vivo. Sci Rep. 2018;8:684 pubmed publisher
    ..Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure ..
  14. Zalewski A, Ma N, Legeza B, Renthal N, Flück C, Pandey A. Vitamin D-Dependent Rickets Type 1 Caused by Mutations in CYP27B1 Affecting Protein Interactions With Adrenodoxin. J Clin Endocrinol Metab. 2016;101:3409-18 pubmed publisher
    ..Mitochondrial cytochrome P450s require adrenodoxin (FDX1) and adrenodoxin reductase. We created models of CYP27B1-FDX1 complex, which revealed negative effects of mutations H441Y and R459L...
  15. Khalil M, Bernhardt R, Hellwig P. Raman and infrared spectroscopic evidence for the structural changes of the 2Fe2S cluster and its environment during the interaction of adrenodoxin and adrenodoxin reductase. Spectrochim Acta A Mol Biomol Spectrosc. 2017;183:298-305 pubmed publisher
    ..we investigated the interaction of two proteins involved in electron transfer, adrenodoxin (Adx) and adrenodoxin reductase (AdR) by using Raman and infrared spectroscopies...
  16. Xiong S, Wang Y, Yao M, Liu H, Zhou X, Xiao W, et al. Cell foundry with high product specificity and catalytic activity for 21-deoxycortisol biotransformation. Microb Cell Fact. 2017;16:105 pubmed publisher
    ..to construct our biocatalyst by co-expressing heterologous CYP11B1 together with bovine adrenodoxin and adrenodoxin reductase. Through screening CYP11B1s (with mutagenesis at N-terminus) from nine sources, Homo sapiens CYP11B1 ..
  17. Bhaduri A, Ungewickell A, Boxer L, Lopez Pajares V, Zarnegar B, Khavari P. Network Analysis Identifies Mitochondrial Regulation of Epidermal Differentiation by MPZL3 and FDXR. Dev Cell. 2015;35:444-57 pubmed publisher
    ..MPZL3 protein localized to mitochondria, where it interacted with FDXR, which was itself also found to be essential for differentiation...
  18. Ehrhardt M, Gerber A, Hannemann F, Bernhardt R. Expression of human CYP27A1 in B. megaterium for the efficient hydroxylation of cholesterol, vitamin D3 and 7-dehydrocholesterol. J Biotechnol. 2016;218:34-40 pubmed publisher
    ..The human mitochondrial cytochrome P450CYP27A1 was co-expressed with its redox partners adrenodoxin reductase (Adr) and adrenodoxin (Adx)...
  19. Zhang J, Wang C, Chen X, Takada M, Fan C, Zheng X, et al. EglN2 associates with the NRF1-PGC1α complex and controls mitochondrial function in breast cancer. EMBO J. 2015;34:2953-70 pubmed publisher
    ..an activator complex with PGC1α and NRF1 on chromatin, EglN2 promotes the transcription of ferridoxin reductase (FDXR) and maintains mitochondrial function...
  20. Gerber A, Kleser M, Biedendieck R, Bernhardt R, Hannemann F. Functionalized PHB granules provide the basis for the efficient side-chain cleavage of cholesterol and analogs in recombinant Bacillus megaterium. Microb Cell Fact. 2015;14:107 pubmed publisher
    ..poly(3-hydroxybutyrate) (PHB) bodies and that the membrane proteins CYP11A1 and its redox partner adrenodoxin reductase (AdR) are likewise localized to their surrounding phospholipid/protein monolayer...
  21. Solish S, Picado Leonard J, Morel Y, Kuhn R, Mohandas T, Hanukoglu I, et al. Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen----q25 are expressed in steroidogenic tissues. Proc Natl Acad Sci U S A. 1988;85:7104-8 pubmed
    b>Adrenodoxin reductase is a mitochondrial flavoprotein that receives electrons from NADPH, thus initiating the electron-transport chain serving mitochondrial cytochromes P450...
  22. Muller J, Lapko A, Bourenkov G, Ruckpaul K, Heinemann U. Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis. J Biol Chem. 2001;276:2786-9 pubmed
    ..hydroxylating system of adrenal cortex mitochondria consists of the membrane-attached NADPH-dependent adrenodoxin reductase (AR), the soluble one-electron transport protein adrenodoxin (Adx), and a membrane-integrated cytochrome ..
  23. Gonzalez M, Robins D. Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that facilitates recruitment of SRC-1. J Biol Chem. 2001;276:6420-8 pubmed
  24. Tuckey R, Headlam M. Placental cytochrome P450scc (CYP11A1): comparison of catalytic properties between conditions of limiting and saturating adrenodoxin reductase. J Steroid Biochem Mol Biol. 2002;81:153-8 pubmed
    ..Cytochrome P450scc activity is in turn limited by the concentration of adrenodoxin reductase (AR) in placental mitochondria...
  25. Liu G, Chen X. The ferredoxin reductase gene is regulated by the p53 family and sensitizes cells to oxidative stress-induced apoptosis. Oncogene. 2002;21:7195-204 pubmed
    ..Ferredoxin Reductase (protein, FR; gene, FDXR) transfers electron from NADPH to cytochrome P450 via ferredoxin in mitochondria...
  26. Peng Y, Shinde D, Valencia C, Mo J, Rosenfeld J, Truitt Cho M, et al. Biallelic mutations in the ferredoxin reductase gene cause novel mitochondriopathy with optic atrophy. Hum Mol Genet. 2017;26:4937-4950 pubmed publisher
    ..signs of mitochondriopathy and identified 17 individuals from 13 unrelated families with recessive mutations in FDXR, encoding the mitochondrial membrane-associated flavoprotein ferrodoxin reductase required for electron transport ..
  27. Wang C, Yang J, Hao Z, Gong C, Tang L, Xu Y, et al. Suppression of progesterone synthesis in human trophoblast cells by fine particulate matter primarily derived from industry. Environ Pollut. 2017;231:1172-1180 pubmed publisher
    ..Subsequently, the downstream molecules of steroidogenesis, such as ferredoxin reductase (FDXR), CYP11A1 (encoded P450scc), and 3β-Hydroxysteroid dehydrogenase type 1 (3β-HSD1), were inhibited...
  28. Ershov P, Mezentsev Y, Gilep A, Usanov S, Buneeva O, Medvedev A, et al. Isatin-induced increase in the affinity of human ferrochelatase and adrenodoxin reductase interaction. Protein Sci. 2017;26:2458-2462 pubmed publisher
    ..M) increase affinity of interactions between human recombinant ferrochelatase (FECH) and NADPH-dependent adrenodoxin reductase (ADR)...
  29. Efimova V, Isaeva L, Makeeva D, Rubtsov M, Novikova L. Expression of Cholesterol Hydroxylase/Lyase System Proteins in Yeast S. cerevisiae Cells as a Self-Processing Polyprotein. Mol Biotechnol. 2017;59:394-406 pubmed publisher
    ..cholesterol hydroxylase/lyase (CHL) system proteins-cytochrome P450scc (CYP11A1), adrenodoxin (Adx) and adrenodoxin reductase (AdR), that are fused into a single ORF using FMDV 2A nucleotide sequences...
  30. Zhang Y, Qian Y, Zhang J, Yan W, Jung Y, Chen M, et al. Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2. Genes Dev. 2017;31:1243-1256 pubmed publisher
    Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters...
  31. Araya Z, Hosseinpour F, Bodin K, Wikvall K. Metabolism of 25-hydroxyvitamin D3 by microsomal and mitochondrial vitamin D3 25-hydroxylases (CYP2D25 and CYP27A1): a novel reaction by CYP27A1. Biochim Biophys Acta. 2003;1632:40-7 pubmed
    ..It can be concluded that both CYP27A1 and CYP2D25 are able to carry out multiple hydroxylations of 25-hydroxyvitamin D(3). ..
  32. Pichiorri F, Okumura H, Nakamura T, Garrison P, Gasparini P, Suh S, et al. Correlation of fragile histidine triad (Fhit) protein structural features with effector interactions and biological functions. J Biol Chem. 2009;284:1040-9 pubmed publisher
    ..shown that Fhit tumor suppressor protein interacts with Hsp60 chaperone machinery and ferredoxin reductase (Fdxr) protein...
  33. Shi Y, Ghosh M, Kovtunovych G, Crooks D, Rouault T. Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis. Biochim Biophys Acta. 2012;1823:484-92 pubmed publisher
    ..To further assess the role of the FDX-FDXR system in mammalian iron-sulfur cluster biogenesis, we performed siRNA studies on FDX1 and FDX2, on several human ..
  34. Sparkes R, Klisak I, Miller W. Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23-q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25. DNA Cell Biol. 1991;10:359-65 pubmed
    ..The gene for adrenodoxin, which receives electrons from adrenodoxin reductase and transfers them to P450scc, is on 11q22 while its pseudogenes are on 20q11-q12...
  35. Linares C, Ferrín G, Aguilar Melero P, González Rubio S, Rodríguez Perálvarez M, Sánchez Aragó M, et al. Sensitivity to anti-Fas is independent of increased cathepsin D activity and adrenodoxin reductase expression occurring in NOS-3 overexpressing HepG2 cells. Biochim Biophys Acta. 2015;1853:1182-94 pubmed publisher
    ..with the expression increase of pro-apoptotic genes and a higher expression/activity of the enzymes adrenodoxin reductase mitochondrial (AR) and cathepsin D (CatD)...
  36. Usanov S, Chernogolov A, Honkakoski P, Lang M, Passanen M, Raunio H, et al. [Cholesterol-hydroxylating cytochrome P-450 from bovine adrenal cortex mitochondria and human placenta: immunochemical properties and structural characteristics]. Biokhimiia. 1990;55:865-77 pubmed
    ..Antibodies against cytochrome P-450scc, adrenodoxin reductase and adrenodoxin from bovine adrenocortical mitochondria were shown to cross-react with corresponding ..
  37. Lin D, Shi Y, Miller W. Cloning and sequence of the human adrenodoxin reductase gene. Proc Natl Acad Sci U S A. 1990;87:8516-20 pubmed
    b>Adrenodoxin reductase (ferrodoxin:NADP+ oxidoreductase, EC 1.18.1.2) is a flavoprotein mediating electron transport to all mitochondrial forms of cytochrome P450...
  38. Sasano H, Sasano N, Okamoto M, Nonaka Y. Immunohistochemical demonstration of adrenodoxin reductase in bovine and human adrenals. Pathol Res Pract. 1989;184:473-9 pubmed
    b>Adrenodoxin reductase (ADR) was purified from bovine adrenocortical mitochondria and specific antibody was raised in rabbits. Immunohistochemical analysis of ADR was performed in the bovine and human adrenals...
  39. Usanov S, Honkakoski P, Lang M, Pasanen M, Pelkonen O, Raunio H. Comparison of the immunochemical properties of human placental and bovine adrenal cholesterol side-chain cleavage enzyme complex. Biochim Biophys Acta. 1989;998:189-95 pubmed
    ..dot-immunobinding analysis, antibodies against bovine adrenocortical cytochrome P-450SCC, adrenodoxin, and adrenodoxin reductase recognized the corresponding proteins in a dose-dependent manner in mitochondrial preparations from human ..
  40. Coghlan V, Vickery L. Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc. J Biol Chem. 1991;266:18606-12 pubmed
    ..This model is consistent with the hypothesis that ferredoxin functions as a mobile shuttle in steroidogenic electron transfer, and it is considered unlikely that a functional ternary complex is formed. ..
  41. Mittal S, Zhu Y, Vickery L. Molecular cloning and sequence analysis of human placental ferredoxin. Arch Biochem Biophys. 1988;264:383-91 pubmed
    ..The N-terminal precursor segment, on the other hand, is considerably diverged from that determined for bovine adrenodoxin, but is similar in overall basicity and the pattern of occurrence of arginine residues. ..
  42. Hanukoglu I. Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme. J Mol Evol. 2017;85:205-218 pubmed publisher
    ..b>Adrenodoxin reductase (AdxR) shares Rossmann fold features with some of these superfamilies but remains in a group of its own in ..
  43. Paul A, Drecourt A, Petit F, Deguine D, Vasnier C, Oufadem M, et al. FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases. Am J Hum Genet. 2017;101:630-637 pubmed publisher
    ..Whole-exome sequencing revealed biallelic mutations in FDXR in affected subjects of each family...
  44. Thiboutot D, Jabara S, McAllister J, Sivarajah A, Gilliland K, Cong Z, et al. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol. 2003;120:905-14 pubmed
    ..In concert with its cofactors, adrenodoxin and adrenodoxin reductase, and the transcription factor steroidogenic factor 1, P450scc converts cholesterol to pregnenolone...
  45. Imamichi Y, Mizutani T, Ju Y, Matsumura T, Kawabe S, Kanno M, et al. Transcriptional regulation of human ferredoxin reductase through an intronic enhancer in steroidogenic cells. Biochim Biophys Acta. 2014;1839:33-42 pubmed publisher
    Ferredoxin reductase (FDXR, also known as adrenodoxin reductase) is a mitochondrial flavoprotein that transfers electrons from NADPH to mitochondrial cytochrome P450 enzymes, mediating the function of an iron-sulfur cluster protein, ..