Longevity control by supersulfide-mediated mitochondrial respiration and regulation of protein quality
Akira Nishimura,
Sunghyeon Yoon,
Tetsuro Matsunaga,
Tomoaki Ida,
Minkyung Jung,
Seiryo Ogata,
Masanobu Morita,
Jun Yoshitake,
Yuka Unno,
Uladzimir Barayeu,
Tsuyoshi Takata,
Hiroshi Takagi,
Hozumi Motohashi,
Albert van der Vliet,
Takaaki Akaike
Affiliations
Akira Nishimura
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan
Sunghyeon Yoon
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Tetsuro Matsunaga
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Tomoaki Ida
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan; Organization for Research Promotion, Osaka Metropolitan University, Osaka, Japan
Minkyung Jung
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Seiryo Ogata
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Masanobu Morita
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Jun Yoshitake
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Yuka Unno
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Uladzimir Barayeu
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Tsuyoshi Takata
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
Hiroshi Takagi
Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan
Hozumi Motohashi
Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
Albert van der Vliet
Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA
Takaaki Akaike
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan; Corresponding author. Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Supersulfides, which are defined as sulfur species with catenated sulfur atoms, are increasingly being investigated in biology. We recently identified pyridoxal phosphate (PLP)-dependent biosynthesis of cysteine persulfide (CysSSH) and related supersulfides by cysteinyl-tRNA synthetase (CARS). Here, we investigated the physiological role of CysSSH in budding yeast (Saccharomyces cerevisiae) by generating a PLP-binding site mutation K109A in CRS1 (the yeast ortholog of CARS), which decreased the synthesis of CysSSH and related supersulfides and also led to reduced chronological aging, effects that were associated with an increased endoplasmic reticulum stress response and impaired mitochondrial bioenergetics. Reduced chronological aging in the K109A mutant could be rescued by using exogenous supersulfide donors. Our findings indicate important roles for CARS in the production and metabolism of supersulfides—to mediate mitochondrial function and to regulate longevity.
