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Affiliation |
Graduate School of Medicine Comprehensive Center for Infectious Disease Control |
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Laboratory Phone number |
+81-18-801-7129 |
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Laboratory Fax number |
+81-18-801-7129 |
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Homepage URL |
MATSUNAGA Tetsuro
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Research Interests 【 display / non-display 】
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infectious disease
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Sulfur biology
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Virology
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Bacteriology
Graduate School 【 display / non-display 】
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-2011.03
Tottori University Graduate School, Division of Agricltural Sciences Doctor's Course Completed
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-2008.03
Yamaguchi University Graduate School, Division of Agriculture Master's Course Completed
Campus Career 【 display / non-display 】
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2025.04-Now
Akita University Graduate School of Medicine Comprehensive Center for Infectious Disease Control Professor
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2024.04-2025.03
Akita University Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases Professor
External Career 【 display / non-display 】
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2025.04
Comprehensive Center for Infectious Disease Control, Graduate School of Medicine, Akita University Professor
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2025.02
Shimadzu × Tohoku University Supersulfides Life Science Co-creation Research Center
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2024.04
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine Lecturer
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2024.04
Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University Professor
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2024.03
Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine Senior Assistant Professor
Research Areas 【 display / non-display 】
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Life Science / Applied microbiology
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Life Science / Virology
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Life Science / Bacteriology
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Life Science / Medical biochemistry
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Life Science / Bacteriology
Research Achievements 【 display / non-display 】
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Supersulfide metabolome of exhaled breath condensate applied as diagnostic biomarkers for esophageal cancer.
Seji Asamitsu, Yohei Ozawa, Hiroshi Okamoto, Seiryo Ogata, Tetsuro Matsunaga, Jun Yoshitake, Kazuki Fusegawa, Yusuke Taniyama, Chiaki Sato, Hirotaka Ishida, Takaaki Abe, Hozumi Motohashi, Takaaki Akaike, Takashi Kamei
Cancer science 2025.02 [Refereed]
Research paper (journal)
Early detection of esophageal cancer is essential for esophagogastroduodenoscopy and histopathological diagnosis. However, endoscopic examinations are sometimes invasive, which limits their clinical application and compliance, and traditional blood tumor markers are unsuitable for cancer screening. The current study aimed to evaluate the usefulness of sulfur metabolites as new biomarkers for esophageal cancer using blood samples and exhaled breath condensate (EBC), which can be readily obtained and is non-invasive. We collected EBC and plasma samples from 50 patients with esophageal cancer and 30 healthy controls. Sulfur metabolome analysis using tandem mass spectrometry was performed to compare the metabolic profile between the two groups. Supersulfide metabolic profiles were different between the two cohorts. Supersulfide metabolome analysis showed that cysteine hydropersulfide (CysSSH) and homocysteine hydropersulfide (HomoCysSSH) were increased in the plasma of patients with esophageal cancer. Elevated levels of HomoCysSSH could distinguish patients with esophageal cancer from healthy subjects (area under the curve [AUC]: 0.93, sensitivity: 89%, specificity: 96%). Interestingly, we also detected an elevation of supersulfides in the EBC analysis. CysSSH levels significantly increased in the EBC recovered from patients with esophageal cancer (AUC: 0.71, sensitivity: 60%, specificity: 96%). In addition, the observed level was correlated with that of HomoCysSSH in the plasma (r = 0.27). Supersulfides, such as CysSSH and HomoCysSSH, are potential biomarkers for detecting esophageal cancer. CysSSH from EBC may serve as a valuable non-invasive biomarker with similar detection ability but with superior precision and convenience compared with the currently available blood biomarkers.
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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.
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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.
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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.
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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.
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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]
The research area of persulfides and polysulfides has piqued the interest of many scientists worldwide. Numerous attempts have been made to understand the nature of reactive sulfur species particularly biological polysulfides and supersulfides (RSnSH). Appreciable amounts of the endogenous RSnSH cysteine hydropersulfide were discovered in various organisms. The moonlighting function of mitochondrial cysteinyl-tRNA synthetase as a persulfide synthase was also discovered. This enzyme was thought to be the major player in the biogenesis of endogenous low-molecular-weight RSnSH, and, as one important function, it integrates RSnSH into proteins. Several studies indicated that RSnSH is highly relevant to various biological functions, from cell signaling to electrophilic regulation. In this review, we focus on highlighting the potential roles of endogenous RSnSH as part of the critical biological detoxification mechanism.
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新興感染症菌Helicobacter cinaediの骨髄内の潜伏感染と細胞内寄生性の分子機構の解明
松永 哲郎, 西村 明, 守田 匡伸, 井田 智章, 津々木 博康, 澤 智裕, 河村 好章, 赤池 孝章
日本細菌学雑誌 ( 日本細菌学会 ) 74 ( 1 ) 104 - 104 2019.03
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新興感染症菌Helicobacter cinaediの骨髄内における潜伏感染と細胞内寄生性の解析
松永哲郎, 西村明, 守田匡伸, 藤井重元, 井田智章, 澤智裕, 河村好章, 赤池孝章
日本細菌学雑誌(Web) ( 日本細菌学会 ) 73 ( 1 ) 117(J‐STAGE) - 117 2018.02
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新興感染症菌Helicobacter cinaediの骨髄内における潜伏感染と細胞内寄生性の解析
松永 哲郎, 西村 明, 守田 匡伸, 藤井 重元, 井田 智章, 澤 智裕, 河村 好章, 赤池 孝章
日本細菌学雑誌 ( 日本細菌学会 ) 73 ( 1 ) 117 - 117 2018.02
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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.
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Books 【 display / non-display 】
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Breathomics for respiratory viral infection.
Tetsuro Matsunaga, Tianli Zhang, Takaaki Akaike
2024.09
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Natural elements as origin of life and evolution: Prologue of supersulfide biology
2023.01
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Chemistry and metabolism of supersulfides
Akaike Takaaki, Matsunaga Tetsuro, Takata Tsuyoshi
2021.10
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Novel biosynthetic pathway and metabolism regulation of reactive sulfur species.
高田剛, 松永哲郎, 赤池孝章
2020.10
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Exploring supersulfide that mediates energy metabolism and redox signaling
Grant-in-Aid for Scientific Research(S)
Project Year： 2024.04 - 2029.03
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Exploring supersulfide that mediates energy metabolism and redox signaling
Grant-in-Aid for Scientific Research(S)
Project Year： 2024.04 - 2029.03
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Exploring supersulfide that mediates energy metabolism and redox signaling
Grant-in-Aid for Scientific Research(S)
Project Year： 2024.04 - 2029.03
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Grant-in-Aid for Scientific Research(C)
Project Year： 2023.04 - 2026.03
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Grant-in-Aid for Scientific Research(C)
Project Year： 2023.04 - 2026.03
Presentations 【 display / non-display 】
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Supersulfides-mediated mitochondrial energy metabolism in mammals
Tetsuro Matsunaga
Nitric Oxide Gordon Research Conference; Nitric Oxide and Sulfide in Redox Signaling and Medicine (Ventura, California) 2025.02 - 2025.02
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Quantitative detection of supersulfides using mass spectrometry
Tetsuro Matsunaga, Takaaki Akaike
2024.12 - 2024.12
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Cyclo-octa-sulfur-mediated mitochondrial energy metabolism in mammals
Tetsuro Matsunaga, Uladzimir Barayeu, Takayuki Shimizu, Zhang Tianli, Masanobu Morita, Seiryo Ogata, Minkyung Jung, Shinji Masuda, Michito Yoshizawa, Hozumi Motohashi, Takaaki Akaike
2024.11 - 2024.11
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Cyclo-octa-sulfur contributes to energy metabolism in mitochondria
Tetsuro Matsunaga, Uladzimir Barayeu, Masanobu Morita, Seiryo Ogata, Minkyung Jung, Tianli Zhang, Tsuyoshi Takata, Michito Yoshizawa, Hozumi Motohashi, Takaaki Akaike
The 13th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide 2024 (Stockholm) 2024.08 - 2024.08
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Supersulfides-driven mitochondrial energy metabolism in mammals
Tetsuro Matsunaga
2024 Gordon Research Conference on: Thiol-Based Redox Regulation and Signaling (Barcelona) 2024.07 - 2024.07
Media Report 【 display / non-display 】
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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.