NO-inducible nitrosothionein mediates NO removal in tandem with thioredoxin

Nat Chem Biol. 2013 Oct;9(10):657-63. doi: 10.1038/nchembio.1316. Epub 2013 Aug 18.


Nitric oxide (NO) is a toxic reactive nitrogen species that induces microbial adaption mechanisms. Screening a genomic DNA library identified a new gene, ntpA, that conferred growth tolerance upon Aspergillus nidulans against exogenous NO. The gene encoded a cysteine-rich 23-amino-acid peptide that reacted with NO and S-nitrosoglutathione to generate an S-nitrosated peptide. Disrupting ntpA increased amounts of cellular S-nitrosothiol and NO susceptibility. Thioredoxin and its reductase denitrosated the S-nitrosated peptide, decreased cellular S-nitrosothiol and conferred tolerance against NO, indicating peptide-mediated catalytic NO removal. The peptide binds copper(I) in vitro but is dispensable for metal tolerance in vivo. NO but not metal ions induced production of the peptide and ntpA transcripts. We discovered that the thionein family of peptides has NO-related functions and propose that the new peptide be named NO-inducible nitrosothionein (iNT). The ubiquitous distribution of iNT-like polypeptides constitutes a potent NO-detoxifying mechanism that is conserved among various organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus nidulans / genetics
  • Aspergillus nidulans / growth & development
  • Aspergillus nidulans / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Genes, Fungal / genetics
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Reactive Nitrogen Species / metabolism
  • S-Nitrosoglutathione / metabolism*
  • Thioredoxins / metabolism*


  • Fungal Proteins
  • Reactive Nitrogen Species
  • Nitric Oxide
  • Thioredoxins
  • S-Nitrosoglutathione