Biological hydropersulfides and related polysulfides – a new concept and perspective in redox biology

Jon M. Fukuto, Louis J. Ignarro, Peter Nagy, David A. Wink, Christopher G. Kevil, Martin Feelisch, Miriam M. Cortese-Krott, Christopher L. Bianco, Yoshito Kumagai, Adrian J. Hobbs, Joseph Lin, Tomoaki Ida, Takaaki Akaike

Research output: Contribution to journalReview articlepeer-review

100 Citations (Scopus)


The chemical biology of thiols (RSH, e.g., cysteine and cysteine-containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection, and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSS n H, RSS n R, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSS n H. RSSH of cysteine (Cys-SSH) has been found to be prevalent in mammalian systems along with Cys-SSH-containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys-SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles.

Original languageEnglish
Pages (from-to)2140-2152
Number of pages13
JournalFEBS Letters
Issue number12
Publication statusPublished - 2018 Jun


  • cysteine persulfides
  • hydropersulfides
  • translational polysulfidation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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