Chemical Biology of Hydropersulfides and Related Species: Possible Roles in Cellular Protection and Redox Signaling

Significance: For >20 years, physiological signaling associated with the endogenous generation of hydrogen sulfide (H₂S) has been of significant interest. Despite its presumed importance, the biochemical mechanisms associated with its actions have not been elucidated. Recent Advances: Recently it has been found that H₂S-related or derived species are highly prevalent in mammalian systems and that these species may be responsible for some, if not the majority, of the biological actions attributed to H₂S. One of the most prevalent and intriguing species are hydropersulfides (RSSH), which can be present at significant levels. Indeed, it appears that H₂S and RSSH are intimately linked in biological systems and likely to be mutually inclusive. Critical Issues: The fact that H₂S and polysulfides such as RSSH are present simultaneously means that the biological actions previously assigned to H₂S can be instead because of the presence of RSSH (or other polysulfides). Thus, it remains possible that hydropersulfides are the biological effectors, and H₂S serves, to a certain extent, as a marker for persulfides and polysulfides. Addressing this possibility will to a large extent be based on the chemistry of these species. Future Directions: Currently, it is known that persulfides possess unique and novel chemical properties that may explain their biological prevalence. However, significantly more work will be required to establish the possible physiological roles of these species. Moreover, an understanding of the regulation of their biosynthesis and degradation will become important topics in piecing together their biology.