N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H 2 S and Sulfane Sulfur Production

Daria Ezeriņa, Yoko Takano, Kenjiro Hanaoka, Yasuteru Urano, Tobias P. Dick

Research output: Contribution to journalArticlepeer-review

241 Citations (Scopus)


The cysteine prodrug N-acetyl cysteine (NAC) is widely used as a pharmacological antioxidant and cytoprotectant. It has been reported to lower endogenous oxidant levels and to protect cells against a wide range of pro-oxidative insults. As NAC itself is a poor scavenger of oxidants, the molecular mechanisms behind the antioxidative effects of NAC have remained uncertain. Here we show that NAC-derived cysteine is desulfurated to generate hydrogen sulfide, which in turn is oxidized to sulfane sulfur species, predominantly within mitochondria. We provide evidence suggesting the possibility that sulfane sulfur species produced by 3-mercaptopyruvate sulfurtransferase and sulfide:quinone oxidoreductase are the actual mediators of the immediate antioxidative and cytoprotective effects provided by NAC. N-Acetyl cysteine (NAC), by itself a poor scavenger of oxidants, is converted inside cells to yield sulfane sulfur species, which are very potent scavengers of oxidants. This conversion may account for many of the antioxidative effects provided by NAC which have hitherto remained unexplained.

Original languageEnglish
Pages (from-to)447-459.e4
JournalCell Chemical Biology
Issue number4
Publication statusPublished - 2018 Apr 19
Externally publishedYes


  • N-acetyl cysteine
  • antioxidant
  • cysteine
  • cytoprotection
  • hydrogen sulfide
  • hydropersulfides
  • roGFP2
  • stress resistance
  • sulfane sulfur
  • sulfide:quinone oxidoreductase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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