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.

Details

Title
Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics
Author
Akaike, Takaaki 1 ; Ida, Tomoaki 1 ; Fan-Yan, Wei 2 ; Nishida, Motohiro 3 ; Kumagai, Yoshito 4 ; Alam, Md Morshedul 5 ; Ihara, Hideshi 6 ; Sawa, Tomohiro 7 ; Matsunaga, Tetsuro 1 ; Kasamatsu, Shingo 1 ; Nishimura, Akiyuki 8 ; Morita, Masanobu 1 ; Tomizawa, Kazuhito 2 ; Nishimura, Akira 1 ; Watanabe, Satoshi 9   VIAFID ORCID Logo  ; Inaba, Kenji 9 ; Shima, Hiroshi 10 ; Tanuma, Nobuhiro 10 ; Jung, Minkyung 1 ; Fujii, Shigemoto 1 ; Watanabe, Yasuo 11 ; Ohmuraya, Masaki 12 ; Nagy, Péter 13 ; Feelisch, Martin 14 ; Fukuto, Jon M 15 ; Motohashi, Hozumi 5   VIAFID ORCID Logo 

 Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan 
 Department of Molecular Physiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan 
 Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Translational Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan 
 Environmental Biology Section, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan 
 Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan 
 Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka, Japan 
 Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan 
 Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan 
 Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan 
10  Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Natori, Japan 
11  Laboratory of Pharmacology, Showa Pharmaceutical University, Tokyo, Japan 
12  Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan 
13  Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary 
14  Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton, UK 
15  Department of Chemistry, Sonoma State University, Rohnert Park, CA, USA 
Pages
1-15
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1956480394
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.