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Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics

Akaike, Takaaki, Ida, Tomoaki, Wei, Fan-yan, Nishida, Motohiro, Kumagai, Yoshito, Alam, Md. Morshedul, Ihara, Hideshi, Sawa, Tomohiro, Matsunaga, Tetsuro, Kasamatsu, Shingo, Nishimura, Akiyuki, Morita, Masanobu, Tomizawa, Kazuhito, Nishimura, Akira, Watanabe, Satoshi, Inaba, Kenji, Shima, Hiroshi, Tanuma, Nobuhiro, Jung, Minkyung, Fujii, Shigemoto, Watanabe, Yasuo, Ohmuraya, Masaki, Nagy, Péter, Feelisch, Martin, Fukuto, Jon M. and Motohashi, Hozumi (2017) Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics Nature Communications, 8, (1)

Record type: Article


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.

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Accepted/In Press date: 29 August 2017
e-pub ahead of print date: 27 October 2017
Published date: 1 December 2017


Local EPrints ID: 415191
PURE UUID: d16804a4-1502-4e12-a368-86b20b43a75a
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 02 Nov 2017 17:30
Last modified: 13 Nov 2017 23:15

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Author: Takaaki Akaike
Author: Tomoaki Ida
Author: Fan-yan Wei
Author: Motohiro Nishida
Author: Yoshito Kumagai
Author: Md. Morshedul Alam
Author: Hideshi Ihara
Author: Tomohiro Sawa
Author: Tetsuro Matsunaga
Author: Shingo Kasamatsu
Author: Akiyuki Nishimura
Author: Masanobu Morita
Author: Kazuhito Tomizawa
Author: Akira Nishimura
Author: Satoshi Watanabe
Author: Kenji Inaba
Author: Hiroshi Shima
Author: Nobuhiro Tanuma
Author: Minkyung Jung
Author: Shigemoto Fujii
Author: Yasuo Watanabe
Author: Masaki Ohmuraya
Author: Péter Nagy
Author: Martin Feelisch ORCID iD
Author: Jon M. Fukuto
Author: Hozumi Motohashi

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