Mammalian Selenoprotein Thioredoxin-glutathione Reductase

Authors

Dan Su, University of Nebraska-Lincoln
Sergey V. Novoselov, University of Nebraska-Lincoln
Qi-An Sun, University of Nebraska-Lincoln
Mohamed E. Moustafa, NCI, National Institutes of Health, Bethesda, Maryland
You Zhou, University of Nebraska-LincolnFollow
Richard Oko, Queen’s University, Kingston, Ontario K7L 3N6, Canada
Dolph L. Hatfield, NCI, National Institutes of Health, Bethesda, MarylandFollow
Vadim N. Gladyshev, University of Nebraska-LincolnFollow

Date of this Version

July 2005

Comments

Published in THE JOURNAL OF BIOLOGICAL CHEMISTRY, Vol. 280, No. 28, Issue of July 15, pp. 26491–26498, 2005.

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 in male reproduction.