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

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133 Scopus citations

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

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Su, D., Novoselov, S. V., Sun, Q. A., Moustafa, M. E., Zhou, Y., Oko, R., Hatfield, D. L., & Gladyshev, V. N. (2005). Mammalian selenoprotein thioredoxin-glutathione reductase: Roles in bisulfide bond formation and sperm maturation. Journal of Biological Chemistry, 280(28), 26491-26498. https://doi.org/10.1074/jbc.M503638200