Identification and characterization of alternatively transcribed form of peroxiredoxin IV gene that is specifically expressed in spermatids of postpubertal mouse testis

J Biol Chem. 2011 Nov 11;286(45):39002-12. doi: 10.1074/jbc.M111.257220. Epub 2011 Aug 11.


2-Cysteine (Cys) peroxiredoxins (Prxs), which include mammalian Prxs I-IV, possess two conserved Cys residues that are readily oxidized by H(2)O(2) to form a disulfide. In the case of Prx I-III, the disulfide is reduced by thioredoxin, thus enabling these proteins to function as peroxidases. Prx IV was shown previously to be synthesized as a 31-kDa polypeptide with an NH(2)-terminal signal peptide that is subsequently cleaved to generate a 27-kDa form of the protein that is localized to the endoplasmic reticulum. A form of Prx IV, larger than 27 kDa revealed by immunoblot analysis was suggested to represent the unprocessed, 31-kDa form, but this larger form was detected only in spermatids of the postpubertal testis. We now show that the larger form of Prx IV (here designated Prx IV-L) detected in the testis is actually a product of alternative transcription of the Prx IV gene that is encoded by newly identified exon 1A together with exons 2-7 that are shared with the 27-kDa form (designated Prx IV-S). Prx IV-L was detected in spermatids but not in mature sperm, it could form disulfide-linked dimers but not higher order oligomers via oxidation, and it was resistant to hyperoxidation unless additional reductant was added, suggesting that its peroxidase activity is limited in vivo. Phylogenetic analysis showed that the Prx IV-S gene is present in all vertebrates examined, whereas the Prx IV-L gene was detected only in placental mammals. We suggest that Prx IV-L functions as an H(2)O(2) sensor that mediates protein thiol oxidation required for the maturation of spermatozoa in placental mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exons / physiology*
  • Hydrogen Peroxide / metabolism
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Male
  • Mice
  • Oxidation-Reduction
  • Peroxiredoxins / biosynthesis*
  • Peroxiredoxins / genetics
  • Phylogeny
  • Sexual Maturation / physiology*
  • Spermatids / cytology
  • Spermatids / enzymology*
  • Testis / cytology
  • Testis / enzymology*
  • Transcription, Genetic / physiology*


  • Isoenzymes
  • Hydrogen Peroxide
  • Peroxiredoxins