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

Abstract

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 (RSSnH, RSSnR, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSSnH. 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.

OxyR senses reactive sulfane sulfur and activates genes for its removal in Escherichia coli

“…These four enzymes are all involved in sulfane sulfur generation. Whereas, H 2 O 2 stress significantly upregulated the expression of CARS and SodA, consistent with the report that proteins involved in sulfane sulfur biosynthesis are induced under oxidative stress because sulfane sulfur functions as antioxidants (Fukuto et al, 2018) . GrxA, TrxC, and KatG were similarly upregulated by H 2 S n and H 2 O 2 stress; Trx A and TrxB were not obviously affected by H 2 S n stress, but H 2 O 2 stress upregulated them (Fig.…”

Extended hypoxia‐mediated H2S production provides for long‐term oxygen sensing

“…It is also possible that H 2 S may be produced by one or several other “unconventional” pathways that are unaffected by these inhibitors and are independent of Cys. These have been reviewed in detail and only a few of the potentially more relevant pathways are briefly described below and summarized in Figure B.…”

“…[43][44][45] It is also possible that H 2 S may be produced by one or several other "unconventional" pathways that are unaffected by these inhibitors and are independent of Cys. These have been reviewed in detail 36,46 and only a few of the potentially more relevant pathways are briefly described below and summarized in Figure 10B. The dynamic equilibrium between H 2 S and polysulphides provides ample opportunity to affect intracellular concentrations of each and as there are multiple mechanisms for H 2 S production that are independent of CBS, CSE and 3-MST it is not surprising that we could not block H 2 S production.…”

Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

“…A fall in oxygen can also increase H 2 S via other mechanisms. There is a large store of polysulfides in cells [13][14][15][16][17]. A fall in oxygen will increase the reducing environment in cells and reductants such as ascorbate and thioredoxin can then release H 2 S from polysulfides and thiosulfate [18][19][20][21].…”