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 Fujii & 6 others Yasuo Watanabe, Masaki Ohmuraya, Péter Nagy, Martin Feelisch, Jon M. Fukuto, Hozumi Motohashi

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.

Original languageEnglish
Article number1177
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

Fingerprint

cysteinyl-tRNA synthetase
cysteine
Energy Metabolism
Cysteine
Cysteine Synthase
Cells
Hydrogen Sulfide
Gene encoding
Oxidative stress
Mitochondrial Genes
Escherichia coli Proteins
Biosynthesis
biological evolution
Organelle Biogenesis
biosynthesis
hydrogen sulfide
Escherichia coli
Oxidation-Reduction
Escherichia
Oxidative Stress

ASJC Scopus subject areas

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

Cite this

Akaike, T., Ida, T., Wei, F. Y., Nishida, M., Kumagai, Y., Alam, M. 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

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.; Motohashi, Hozumi.

In: Nature Communications, Vol. 8, No. 1, 1177, 01.12.2017.

Research output: Contribution to journalArticle

Akaike, T, Ida, T, Wei, FY, Nishida, M, Kumagai, Y, Alam, MM, 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, JM & Motohashi, H 2017, 'Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics', Nature Communications, vol. 8, no. 1, 1177. https://doi.org/10.1038/s41467-017-01311-y
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. ; Motohashi, Hozumi. / Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. In: Nature Communications. 2017 ; Vol. 8, No. 1.
@article{853c36be6e464069930f739d7cf27a8f,
title = "Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics",
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.",
author = "Takaaki Akaike and Tomoaki Ida and Wei, {Fan Yan} and Motohiro Nishida and Yoshito Kumagai and Alam, {Md Morshedul} and Hideshi Ihara and Tomohiro Sawa and Tetsuro Matsunaga and Shingo Kasamatsu and Akiyuki Nishimura and Masanobu Morita and Kazuhito Tomizawa and Akira Nishimura and Satoshi Watanabe and Kenji Inaba and Hiroshi Shima and Nobuhiro Tanuma and Minkyung Jung and Shigemoto Fujii and Yasuo Watanabe and Masaki Ohmuraya and P{\'e}ter Nagy and Martin Feelisch and Fukuto, {Jon M.} and Hozumi Motohashi",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41467-017-01311-y",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics

AU - Akaike, Takaaki

AU - Ida, Tomoaki

AU - Wei, Fan Yan

AU - Nishida, Motohiro

AU - Kumagai, Yoshito

AU - Alam, Md Morshedul

AU - Ihara, Hideshi

AU - Sawa, Tomohiro

AU - Matsunaga, Tetsuro

AU - Kasamatsu, Shingo

AU - Nishimura, Akiyuki

AU - Morita, Masanobu

AU - Tomizawa, Kazuhito

AU - Nishimura, Akira

AU - Watanabe, Satoshi

AU - Inaba, Kenji

AU - Shima, Hiroshi

AU - Tanuma, Nobuhiro

AU - Jung, Minkyung

AU - Fujii, Shigemoto

AU - Watanabe, Yasuo

AU - Ohmuraya, Masaki

AU - Nagy, Péter

AU - Feelisch, Martin

AU - Fukuto, Jon M.

AU - Motohashi, Hozumi

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85031718698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031718698&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-01311-y

DO - 10.1038/s41467-017-01311-y

M3 - Article

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1177

ER -