Enzymatic Regulation and Biological Functions of Reactive Cysteine Persulfides and Polysulfides

Abstract

Cysteine persulfide (CysSSH) and cysteine polysulfides (CysSSnH, n > 1) are cysteine derivatives that have sulfane sulfur atoms bound to cysteine thiol. Advances in analytical methods that detect and quantify persulfides and polysulfides have shown that CysSSH and related species such as glutathione persulfide occur physiologically and are prevalent in prokaryotes, eukaryotes, and mammals in vivo. The chemical properties and abundance of these compounds suggest a central role for reactive persulfides in cell-regulatory processes. CysSSH and related species have been suggested to act as powerful antioxidants and cellular protectants and may serve as redox signaling intermediates. It was recently shown that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase. In addition, we discovered that CARS is involved in protein polysulfidation that is coupled with translation. Mitochondrial activity in biogenesis and bioenergetics is supported and upregulated by CysSSH derived from mitochondrial CARS. In this review article, we discuss the mechanisms of the biosynthesis of CysSSH and related persulfide species, with a particular focus on the roles of CARS. We also review the antioxidative and anti-inflammatory actions of persulfides.

Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm

“…Although it is unclear how the H 2 S donor increases in mitochondrial levels of CARS2, CARS2‐mediated synthesis of cysteine hydropersulfide (CysSSH) can produce H 2 S in the mitochondria and participate in mitochondrial respiration 22 . Further, CysSSH is a nucleophile that can protect against oxidative stress in cells 10,23 . It is possible that exogenous H 2 S donors supplemented the endogenous H 2 S synthesis in diaphragm fibers during prolonged MV 24,25 ; this is a testable hypothesis worthy of future study.…”

Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases

“…Persulfidation regulates fine tune protein function, localization and interaction in cells [36]. It also modulates biological processes, including autophagy, cellular metabolism, inflammation, cell cycle, and cell death under physiological and pathological contexts [37]. It has been shown that the Cys' architecture and spatial arrangement determine if the residue can be persulfonated and the effect on protein function.…”

The impact of gut microbiota metabolites on cellular bioenergetics and cardiometabolic health

“…The range of total sulfide in human feces is 0.2-3.4 mmol/l, averaging at 0.74 mmol/l [20]. H 2 S may exist in a free form or be bound to cysteine thiols as sulfane sulfur [54]. In addition, feces have large sulfide-binding activity and therefore, less than 8% of total sulfide (~ 60 µmol/l) is in the free form [20].…”