Persulfides and the cellular thiol landscape.

Abstract

The biochemistry of sulfur touches on every aspect of cellular biology, from protein structure and function to redox regulation to defense against chemical stress. Over the last decade, posttranslational modification of protein thiols by reactive oxygen or nitrogen species has emerged as a major component of signal transduction, leading to both regulatory and inflammatory responses. A variety of disease states may thus arise as a result of dysregulation in formation of oxygen- and nitrogen-containing messenger molecules or in modification of thiols. For this reason, the pathways, products, and effects of thiol, thiolate, and disulfide modification have been the subject of intense investigation. Understanding of the extent and impact of thiol modification and metabolism has advanced through observation of physiological effects, as well as by in vivo detection of sulfur-based mediators and downstream products. In PNAS, Ida et al. (1) describe a new mass spectrometric method to quantitate low molecular-weight persulfide (RSSH) and polysulfide content in cells and a proteomic/Tag-Switch assay to detect S-polythiolated protein adducts. Their findings suggest that persulfides and polysulfides are reactive species that not only must be included among sulfur-based moieties that regulate oxidative stress and redox signaling, but in fact may be major mediators in this regard.