Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases 

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Research Interests 【 display / non-display

  • infectious disease

  • Sulfur biology

  • Virology

  • Bacteriology

Graduate School 【 display / non-display


    Tottori University  Graduate School, Division of Agricltural Sciences  Doctor's Course  Completed


    Yamaguchi University  Graduate School, Division of Agriculture  Master's Course  Completed

Campus Career 【 display / non-display

  • 2024.04

    Akita University   Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases   Professor  

External Career 【 display / non-display

  • 2024.04

    Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine   Lecturer  

  • 2024.04

    Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University   Professor  

  • 2024.03

    Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine   Senior Assistant Professor  

  • 2013.06

    Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine   Assistant Professor  

Research Areas 【 display / non-display

  • Life Science / Applied microbiology

  • Life Science / Virology

  • Life Science / Bacteriology

  • Life Science / Medical biochemistry

  • Life Science / Bacteriology

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Research Achievements 【 display / non-display

    ◆Original paper【 display / non-display

  • 2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels.

    Qi Cui, Meg Shieh, Tony W Pan, Akiyuki Nishimura, Tetsuro Matsunaga, Shane S Kelly, Shi Xu, Minkyung Jung, Seiryo Ogata, Masanobu Morita, Jun Yoshitake, Xiaoyan Chen, Jerome R Robinson, Wei-Jun Qian, Motohiro Nishida, Takaaki Akaike, Ming Xian

    Nature Communications   15 ( 1 ) 2453 - 2453   2024.03  [Refereed]

    Research paper (journal)  

    Reactive sulfane sulfur species such as persulfides (RSSH) and H2S2 are important redox regulators and closely linked to H2S signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert H2S to HSOH, and then to H2S2 in the presence of excess H2S. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and H2S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H2S donors, the corresponding donors of H2S2 (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.

    DOI PubMed

  • 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

    Redox Biology   69   103018 - 103018   2024.02  [Refereed]

    Research paper (journal)  

    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.

    DOI PubMed

  • Quantitative profiling of supersulfides naturally occurring in dietary meats and beans.

    Shingo Kasamatsu, Ayaka Kinno, Chiharu Miura, Jun-Ichi Hishiyama, Kensuke Fukui, Shoji Kure, Kazunobu Tsumura, Tomoaki Ida, Tetsuro Matsunaga, Takaaki Akaike, Hideshi Ihara

    Analytical Biochemistry   685   115392 - 115392   2024.01  [Refereed]

    Research paper (journal)  

    Sulfur is essential in the inception of life and crucial for maintaining human health. This mineral is primarily supplied through the intake of proteins and is used for synthesizing various sulfur-containing biomolecules. Recent research has highlighted the biological significance of endogenous supersulfides, which include reactive persulfide species and sulfur catenated residues in thiol and proteins. Ingestion of exogenous sulfur compounds is essential for endogenous supersulfide production. However, the content and composition of supersulfides in foods remain unclear. This study investigated the supersulfide profiles of protein-rich foods, including edible animal meat and beans. Quantification of the supersulfide content revealed that natto, chicken liver, and bean sprouts contained abundant supersulfides. In general, the supersulfide content in beans and their derivatives was higher than that in animal meat. The highest proportion (2.15 %) was detected in natto, a traditional Japanese fermented soybean dish. These results suggest that the abundance of supersulfides, especially in foods like natto and bean sprouts, may contribute to their health-promoting properties. Our findings may have significant biological implications and warrant developing novel dietary intervention for the human health-promoting effects of dietary supersulfides abundantly present in protein-rich foods such as natto and bean sprouts.

    DOI PubMed

  • Persulfide biosynthesis conserved evolutionarily in all organisms.

    Seiryo Ogata, Tetsuro Matsunaga, Minkyung Jung, Uladzimir Barayeu, Masanobu Morita, Takaaki Akaike

    Antioxidants & Redox Signaling ( Mary Ann Liebert Inc )  39 ( 13-15 ) 983 - 999   2023.11  [Refereed]

    Research paper (journal)  

    SIGNIFICANCE: Persulfides/polysulfides are sulfur-catenated molecular species (i.e., R-Sn-R', n > 2; R-Sn-H, n > 1, with R = cysteine, glutathione, and proteins), such as cysteine persulfide (CysSSH). These species are abundantly formed as endogenous metabolites in mammalian and human cells and tissues. However, the persulfide synthesis mechanism has yet to be thoroughly discussed. RECENT ADVANCES: We used β-(4-hydroxyphenyl)ethyl iodoacetamide and mass spectrometry to develop sulfur metabolomics, a highly precise, quantitative analytical method for sulfur metabolites. CRITICAL ISSUES: With this method, we detected appreciable amounts of different persulfide species in biological specimens from various organisms, from the domains Bacteria, Archaea, and Eukarya. By using our rigorously quantitative approach, we identified cysteinyl-tRNA synthetase (CARS) as a novel persulfide synthase, and we found that the CysSSH synthase activity of CARS is highly conserved from the domains Bacteria to Eukarya. Because persulfide synthesis is found not only with CARS but also with other sulfotransferase enzymes in many organisms, persulfides/polysulfides are expected to contribute as fundamental elements to substantially diverse biological phenomena. In fact, persulfide generation in higher organisms-i.e., plants and animals-demonstrated various physiological functions that are mediated by redox signaling, such as regulation of energy metabolism, infection, inflammation, and cell death including ferroptosis. FUTURE DIRECTIONS: Investigating CARS-dependent persulfide production may clarify various pathways of redox signaling in physiological and pathophysiological conditions and may thereby promote the development of preventive and therapeutic measures for oxidative stress as well as different inflammatory, metabolic, and neurodegenerative diseases.

    DOI PubMed

  • Presence of Helicobacter cinaedi in atherosclerotic abdominal aortic aneurysmal wall.

    Shinichiro Horii, Hirofumi Sugawara, Hitoshi Goto, Munetaka Hashimoto, Tetsuro Matsunaga, Daijirou Akamatsu, Yuta Tajima, Michihisa Umetsu, Takaaki Akaike, Takashi Kamei

    The Tohoku Journal of Experimental Medicine   261 ( 1 ) 35 - 41   2023.09  [Refereed]

    Research paper (journal)  

    Recently, the relationship between Helicobacter cinaedi (H. cinaedi) infection and several diseases, including cardiovascular and central nervous system disorders, bone and soft tissue disorders, and infectious abdominal aortic aneurysms (AAAs), has been reported. Moreover, H. cinaedi may be associated with arteriosclerosis. In the present study, we investigated the association between H. cinaedi infection and clinically uninfected AAAs. Genetic detection of H. cinaedi in the abdominal aneurysm wall was attempted in 39 patients with AAA undergoing elective open surgery between June 2019 and June 2020. DNA samples extracted from the arterial wall obtained during surgery were analyzed using nested polymerase chain reaction (PCR). The target gene region was the H. cinaedi-specific cytolethal distending toxin subunit B (cdtB). Nine (23.1%) of 39 patients showed positive bands corresponding to H. cinaedi, and further sequencing analyses demonstrated the presence of H. cinaedi DNAs in their aneurysm walls. In contrast, all the non-aneurysm arterial walls in our patients were negative for H. cinaedi. In conclusion, this is the first report of the detection of H. cinaedi in the walls of a clinically non-infectious AAA.

    DOI PubMed

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    ◆Other【 display / non-display

  • A persulfide shield: An endogenous reactive sulfur species in the forefront in the electrophile detoxification pathway

    Hisyam Abdul Hamid, Tsuyoshi Takata, Tetsuro Matsunaga, Takaaki Akaike

    Sulfurtransferases ( Elsevier )    101 - 117   2023.01  [Refereed]


  • Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells

    Motohiro Nishida, Akiyuki Nishimura, Tetsuro Matsunaga, Hozumi Motohashi, Shingo Kasamatsu, Takaaki Akaike

    Free Radical Biology and Medicine ( ELSEVIER SCIENCE INC )  109   132 - 140   2017.08  [Refereed]

    Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. Among electrophiles formed endogenously, 8-nitroguanosine 3’,5’-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease.

    DOI PubMed

  • 腸肝在位Helicobacter感染症研究の最前線 Helicobacter cinaediの持続感染と動脈硬化症の進展・促進機構

    松永 哲郎, 藤井 重元, 澤 智裕, 河村 好章, 赤池 孝章

    日本細菌学雑誌 ( 日本細菌学会 )  72 ( 1 ) 31 - 31   2017.02

  • 細菌のイオウ呼吸はすべての生物種に保存されている:ほ乳類における新しいエネルギー代謝経路・イオウ呼吸の発見

    赤池孝章, 井田智章, 松永哲郎, 守田匡伸, 笠松真吾, 西村明, 藤井重元, 居原秀, JUNG Minkyung, 赤司壮一郎, 澤智裕, 本橋ほづみ

    日本細菌学雑誌(Web) ( 日本細菌学会 )  72 ( 1 ) 98(J‐STAGE) - 98   2017.02


Books 【 display / non-display

Grant-in-Aid for Scientific Research 【 display / non-display

  • Grant-in-Aid for Scientific Research(C)

    Project Year: 2023.04  -  2026.03 

  • Grant-in-Aid for Scientific Research(C)

    Project Year: 2023.04  -  2026.03 

  • Investigation of the strategy used by intestinal parasites to high sulfide concentration environment

    Grant-in-Aid for Scientific Research(B)

    Project Year: 2023.04  -  2026.03 

  • Grant-in-Aid for Scientific Research(C)

    Project Year: 2022.04  -  2025.03 

  • Analysis of molecular mechanism of mitochondrial damage and immune suppression induced by Mycobacterium tuberculosis

    Grant-in-Aid for Scientific Research(B)

    Project Year: 2020.04  -  2023.03 

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Presentations 【 display / non-display

  • Supersulfides-mediated mitochondrial energy metabolism in mammals

    Tetsuro Matsunaga

    The 1st International G-ReXS Conference in Sendai  2024.03  -  2024.03 

  • Cyclo-octasulfur-mediated mitochondrial energy metabolism

    2024.01  -  2024.01 

  • Supersulfides-mediated cellular energy metabolism

    2023.12  -  2023.12 

  • Host defense effect of supersulfides on SARS-CoV-2 infection

    2023.09  -  2023.09 

  • Sulfide:quinone oxidoreductase produces cyclo-octasulfur, S8 that mediate sulfur respiration in mitochondria

    Tetsuro Matsunaga, Masanobu Morita, Tomoaki Ida, Akira Nishimura, Minkyung Jung, Tsuyoshi Takata, Péter Nagy, Ming Xian, Motohiro Nishida, Michito Yoshizawa, Hozumi Motohashi, Takaaki Akaike

    Redox Week in Sendai 2022 / The 12th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide (Sendai)  2022.10  -  2022.10 

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Teaching Experience 【 display / non-display

  • 2013
  • 2013
  • 2012

Media Report 【 display / non-display

  • A common sulfur metabolite having antioxidant activity appears to be formed with the help of an enzyme found in mitochondria, highlighting a potential area of research for future treatments of various diseases.