Biogenesis of reactive sulfur species for signaling by hydrogen sulfide oxidation pathways

The chemical species involved in H2S signaling remain elusive despite the profound and pleiotropic physiological effects elicited by this molecule. The dominant candidate mechanism for sulfide signaling is persulfidation of target proteins. However, the relatively poor reactivity of H2S toward oxidized thiols, such as disulfides, the low concentration of disulfides in the reducing milieu of the cell and the low steady-state concentration of H2S raise questions about the plausibility of persulfide formation via reaction between an oxidized thiol and a sulfide anion or a reduced thiol and oxidized hydrogen disulfide. In contrast, sulfide oxidation pathways, considered to be primarily mechanisms for disposing of excess sulfide, generate a series of reactive sulfur species, including persulfides, polysulfides and thiosulfate, that could modify target proteins. We posit that sulfide oxidation pathways mediate sulfide signaling and that sulfurtransferases ensure target specificity.

Nature Chemical Biology 11, 457–464 (2015) doi:10.1038/nchembio.1834

Received 20 November 2014 Accepted 24 April 2015 Published online 17 June 2015