Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling

Tomoaki Ida, Tomohiro Sawa, Hideshi Ihara, Yukihiro Tsuchiya, Yasuo Watanabe, Yoshito Kumagai, Makoto Suematsu, Hozumi Motohashi, Shigemoto Fujii, Tetsuro Matsunaga, Masayuki Yamamoto, Katsuhiko Ono, Nelmi O. Devarie-Baez, Ming Xian, Jon M. Fukuto, Takaaki Akaike

Research output: Contribution to journalArticlepeer-review

694 Citations (Scopus)


Using methodology developed herein, it is found that reactive per-sulfides and polysulfides are formed endogenously from both small molecule species and proteins in high amounts in mammalian cells and tissues. These reactive sulfur species were biosynthesized by two major sulfurtransferases: cystathionine β-synthase and cystathionine γ-lyase. Quantitation of these species indicates that high concentrations of glutathione persulfide (perhydropersulfide >100 μM) and other cysteine persulfide and polysulfide derivatives in pep-tides/proteins were endogenously produced and maintained in the plasma, cells, and tissues of mammals (rodent and human). It is expected that persulfides are especially nucleophilic and reducing. This view was found to be the case, because they quickly react with H2O2 and a recently described biologically generated electrophile 8-nitroguanosine 3',5'-cyclic monophosphate. These results indicate that persulfides are potentially important signaling/effector species, and because H2S can be generated from persulfide degradation, much of the reported biological activity associated with H2S may actually be that of persulfides. That is, H2S may act primarily as a marker for the biologically active of persulfide species.

Original languageEnglish
Pages (from-to)7606-7611
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
Publication statusPublished - 2014 May 27


  • Electrophilic signaling
  • Hydrogen sulfide
  • Polysulfidomics
  • Thiol redox

ASJC Scopus subject areas

  • General


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