Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics

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

研究成果: Article

108 引用 (Scopus)

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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.

元の言語English
記事番号1177
ジャーナルNature communications
8
発行部数1
DOI
出版物ステータスPublished - 2017 12 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    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., ... Motohashi, H. (2017). Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. Nature communications, 8(1), [1177]. https://doi.org/10.1038/s41467-017-01311-y