The Biological/Physiological Utility of Hydropersulfides (RSSH) and Related Species: What Is Old Is New Again

Significance: Hydrogen sulfide (H2S) is reported to be an important mediator involved in numerous physiological processes. H2S and hydropersulfides (RSSH) species are intimately linked biochemically. Therefore, interest in the mechanisms of the biological activity of H2S has led to investigations of the chemical biology of RSSH since they are likely to coexist in a biological system. Currently it is hypothesized that RSSH may be responsible for a least part of the observed H2S-mediated biology/physiology. Recent Advances: It has been recently touted that thiols (RSH) and RSSH have some important differences in terms of their chemical biology and that the generation of RSSH from RSH is purposeful to exploit these chemical differences as a response to a physiological or biological stress. This transformation may represent an unappreciated/unrecognized biological mechanism for dealing with cellular stresses. Critical Issues: Although recent studies indicate a diverse and potentially important chemical biology associated with RSSH species, these ideas have their foundations in early studies (some over 60 years old). It is vital to recognize the nature of this early work to fully appreciate the current ideas regarding RSSH biology. Importantly, these early studies were performed before the realization of purposeful H2S biosynthesis (before 1996). Future Directions: Taking clues from the past studies of RSSH chemistry and biology, progress in delineating the chemical biology of RSSH will continue. Determination of the possible relevance of RSSH chemical biology to signaling and cellular physiology will be a primary focus of many future studies.

Automated summary

Hydrogen sulfide (H2S) plays a significant role in various physiological processes and is closely related biochemically to hydropersulfides (RSSH). Recent studies suggest that RSSH may interact with H2S in biological systems, providing new insights into the chemical biology of RSSH. The future direction of research will focus on determining the relevance of RSSH chemical biology to signaling and cellular physiology.