Mammalian selenoprotein thioredoxin-glutathione reductase

Roles in bisulfide bond formation and sperm maturation

Dan Su, Sergey V. Novoselov, Qi An Sun, Mohamed E. Moustafa, You Zhou, Richard Oko, Dolph L. Hatfield, Vadim N. Gladyshev

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium n male reproduction.

Original languageEnglish (US)
Pages (from-to)26491-26498
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number28
DOIs
StatePublished - Jul 15 2005

Fingerprint

Sperm Maturation
Selenoproteins
Thioredoxin-Disulfide Reductase
Selenocysteine
Thioredoxins
Disulfides
Oxidation-Reduction
Spermatozoa
Glutaredoxins
Proteins
Mammals
Spermatids
Enzymes
Puberty
Selenium
Glutathione Peroxidase
Isomerization
Sulfhydryl Compounds
Reproduction
Testis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mammalian selenoprotein thioredoxin-glutathione reductase : Roles in bisulfide bond formation and sperm maturation. / Su, Dan; Novoselov, Sergey V.; Sun, Qi An; Moustafa, Mohamed E.; Zhou, You; Oko, Richard; Hatfield, Dolph L.; Gladyshev, Vadim N.

In: Journal of Biological Chemistry, Vol. 280, No. 28, 15.07.2005, p. 26491-26498.

Research output: Contribution to journalArticle

Su, D, Novoselov, SV, Sun, QA, Moustafa, ME, Zhou, Y, Oko, R, Hatfield, DL & Gladyshev, VN 2005, 'Mammalian selenoprotein thioredoxin-glutathione reductase: Roles in bisulfide bond formation and sperm maturation', Journal of Biological Chemistry, vol. 280, no. 28, pp. 26491-26498. https://doi.org/10.1074/jbc.M503638200
Su, Dan ; Novoselov, Sergey V. ; Sun, Qi An ; Moustafa, Mohamed E. ; Zhou, You ; Oko, Richard ; Hatfield, Dolph L. ; Gladyshev, Vadim N. / Mammalian selenoprotein thioredoxin-glutathione reductase : Roles in bisulfide bond formation and sperm maturation. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 28. pp. 26491-26498.
@article{aa983f0088224e6b82f1168e9ca50f99,
title = "Mammalian selenoprotein thioredoxin-glutathione reductase: Roles in bisulfide bond formation and sperm maturation",
abstract = "Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium n male reproduction.",
author = "Dan Su and Novoselov, {Sergey V.} and Sun, {Qi An} and Moustafa, {Mohamed E.} and You Zhou and Richard Oko and Hatfield, {Dolph L.} and Gladyshev, {Vadim N.}",
year = "2005",
month = "7",
day = "15",
doi = "10.1074/jbc.M503638200",
language = "English (US)",
volume = "280",
pages = "26491--26498",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "28",

}

TY - JOUR

T1 - Mammalian selenoprotein thioredoxin-glutathione reductase

T2 - Roles in bisulfide bond formation and sperm maturation

AU - Su, Dan

AU - Novoselov, Sergey V.

AU - Sun, Qi An

AU - Moustafa, Mohamed E.

AU - Zhou, You

AU - Oko, Richard

AU - Hatfield, Dolph L.

AU - Gladyshev, Vadim N.

PY - 2005/7/15

Y1 - 2005/7/15

N2 - Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium n male reproduction.

AB - Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium n male reproduction.

UR - http://www.scopus.com/inward/record.url?scp=22544451578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22544451578&partnerID=8YFLogxK

U2 - 10.1074/jbc.M503638200

DO - 10.1074/jbc.M503638200

M3 - Article

VL - 280

SP - 26491

EP - 26498

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 28

ER -