Year-end Sale % OFF 
Abstract
Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Extensive persulfide formation is apparent in cysteine-containing proteins in Escherichia coli and mammalian cells and is believed to result from post-translational processes involving hydrogen sulfide-related chemistry. Here we demonstrate effective CysSSH synthesis from the substrate l-cysteine, a reaction catalyzed by prokaryotic and mammalian cysteinyl-tRNA synthetases (CARSs). Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. CARSs also catalyze co-translational cysteine polysulfidation and are involved in the regulation of mitochondrial biogenesis and bioenergetics. Investigating CARS-dependent persulfide production may thus clarify aberrant redox signaling in physiological and pathophysiological conditions, and suggest therapeutic targets based on oxidative stress and mitochondrial dysfunction.
Highlights
Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions
In evaluating the physiological rationale for biological CysSSH production, our present study confirmed that cysteine persulfide/polysulfides (CysSSH/CysS–(S)n–H) possess mixed sulfur reactivity—both nucleophilic and electrophilic (Supplementary Figs 1 and 2)—a property that is unique and distinct from that of other simple biologically relevant thiols
CSE and CBS may still play a major role in the CysSSH production via the direct catalytic reaction using cystine as the substrate especially under pathophysiological conditions associated with oxidative and electrophilic stress, where intracellular cystine concentrations are value of CSE3,7,21,40–42
Summary
Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. 4 Department of Translational Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. 6 Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan. 7 Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka 599-8531, Japan. Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton SO16 6YD, UK. Cysteine hydropersulfide (CysSSH) is found physiologically in prokaryotes, eukaryotic cells, and mammalian tissues[1,2]. In cultured cells and tissues The chemical properties and in vivo in mice and abundance of these species suggest a pivotal role for reactive persulfides (i.e., compounds containing an—SSH group) in cell-regulatory processes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
