Publications

• Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics.

  Akaike T., Ida T., Wei F.Y., Nishida M., Kumagai Y., Alam M.M., Ihara H., Sawa T., Matsunaga T., Kasamatsu S., Nishimura A., Morita M., Tomizawa K., Nishimura A., Watanabe S., Inaba K., Shima H., Tanuma N., Jung M., Fujii S., Watanabe Y., Ohmuraya M., Nagy P., Feelisch M., Fukuto J.M., Motohashi H.

  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 ... >> More

  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. << Less

  Nat. Commun. 8:1177-1177(2017) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Persulfide synthases that are functionally coupled with translation mediate sulfur respiration in mammalian cells.

  Fujii S., Sawa T., Motohashi H., Akaike T.

  Cysteine persulfide and polysulfide are produced in cells and exist in abundance in both low MW and protein fractions. However, the mechanism of regulation of the formation of cellular cysteine polysulfides and the physiological functions of cysteine persulfides/polysulfides produced in cells are ... >> More

  Cysteine persulfide and polysulfide are produced in cells and exist in abundance in both low MW and protein fractions. However, the mechanism of regulation of the formation of cellular cysteine polysulfides and the physiological functions of cysteine persulfides/polysulfides produced in cells are not fully understood. We recently demonstrated that cysteinyl-tRNA synthetase (CARS) is a novel cysteine persulfide synthase. CARS is involved in protein polysulfidation that is coupled with translation. In particular, mitochondria function in biogenesis and bioenergetics is also supported and up-regulated by cysteine persulfide derived from mitochondrial CARS (also known as CARS2). Here, we provide an overview of recent advances in reactive persulfide research and our understanding of the mechanisms underlying the formation and the physiological roles of reactive persufides, with a primary focus on the formation of cysteine persulfide by CARS and the most fundamental mitochondrial bioenergetics mediated by persulfides, that is, sulfur respiration. LINKED ARTICLES: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc. << Less

  Br J Pharmacol 176:607-615(2019) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.