Molecular analysis of persulfide dependent signaling involved in bioactive regulation

• Project/Area Number: 18K14650
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Shimizu Takayuki 東京大学, 大学院総合文化研究科, 助教 (90817214)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シグナル制御 / システイン修飾 / 硫化水素 / パースルフィド / 細菌

Outline of Final Research Achievements

Hydrogen sulfide modulates important physiological processes and molecular species containing polysulfur that are called reactive sulfur species (RSS) are the actual signaling molecules. However, RSS signaling and metabolism are not fully understood. To elucidate this, I investigated biochemical properties of RSS sensor protein and RSS metabolic pathways. I revealed that the RSS sensor protein predominantly reacts with specific RSS. Moreover, RSS metabolic enzyme which is related to generation of its RSS was also identified. These results are important to understand the underlying mechanisms of RSS signaling.

Academic Significance and Societal Importance of the Research Achievements

活性イオウ分子種を介したシグナル伝達系の分子基盤の一端を世界で始めた明らかにした本研究成果は、硫化水素・活性イオウ分子種に依存したシグナル伝達の詳細と、その生理的意義を明らかにする上で極めて重要である。また、硫化水素は、脳疾患である統合失調症や心臓疾患である心不全などの様々な疾患に関与することが報告されているため、様々な疾患に対するこれまでにない全く新しいアプローチ・治療法の開発につながることが期待される。したがって、本理学研究の成果は、医学・薬学研究にも大きく波及すると言える。

Research Products

• [Journal Article] Repressor Activity of SqrR, a Master Regulator of Persulfide-Responsive Genes, Is Regulated by Heme Coordination (2021)
  • Author(s): Shimizu T, Hayashi Y, Arai M, McGlynn SE, Masuda T, Masuda S
  • Journal Title: Plant Cell Physiol Volume: 62 Issue: 1 Pages: 100-110
  • DOI: 10.1093/pcp/pcaa144
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Role of Tetrapyrrole- and GUN1-Dependent Signaling on Chloroplast Biogenesis (2021)
  • Author(s): Shimizu T, MasudaT
  • Journal Title: Plants Volume: 10 Issue: 2 Pages: 196-196
  • DOI: 10.3390/plants10020196
  • Peer Reviewed / Open Access
• [Journal Article] Proteomic analysis of haem-binding protein from Arabidopsis thaliana and Cyanidioschyzon merolae (2020)
  • Author(s): Takayuki Shimizu, Rintaro Yasuda, Yui Mukai, Ryo Tanoue, Tomohiro Shimada, Sousuke Imamura, Kan Tanaka, Satoru Watanabe and Tatsuru Masuda
  • Journal Title: Philosophical Transactions of the Royal Society B Volume: 375 Issue: 1801 Pages: 20190488-20190488
  • DOI: 10.1098/rstb.2019.0488
  • Peer Reviewed / Open Access
• [Journal Article] Persulphide-responsive transcriptional regulation and metabolism in bacteria (2019)
  • Author(s): Shimizu Takayuki、Masuda Shinji
  • Journal Title: The Journal of Biochemistry Volume: 167 Pages: 125-132
  • DOI: 10.1093/jb/mvz063
  • Peer Reviewed / Open Access
• [Journal Article] The retrograde signaling protein GUN1 regulates tetrapyrrole biosynthesis. (2019)
  • Author(s): Shimizu, T., Kacprzak, S.M., Mochizuki, N., Nagatani, A., Watanabe, S., Shimada, T., Tanaka, K., Hayashi, Y., Arai, M., Leister, D., Okamoto, H., Terry, M.J., & Masuda, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 116 Issue: 49 Pages: 24900-24906
  • DOI: 10.1073/pnas.1911251116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 硫化水素依存的な生理活性調節におけるパースルフィド応答機構の分子基盤 (2021)
  • Author(s): 清水隆之、増田真二、増田建
  • Organizer: 第62回日本植物生理学会
• [Presentation] 葉緑体形成の制御に関わる葉緑体から核へのシグナル伝達 (2020)
  • Author(s): 清水隆之
  • Organizer: 光合成学会オンラインミニシンポジウム
  • Invited
• [Presentation] 硫化水素による生理活性調節とそのシグナル伝達機構 (2020)
  • Author(s): 清水隆之
  • Organizer: 静岡大学招待講演
  • Invited
• [Presentation] 硫化水素による生理活性調節におけるパースルフィド検知機構の分子基盤 (2020)
  • Author(s): 清水隆之、増田真二、増田建
  • Organizer: 第61回日本植物生理学会
• [Presentation] 硫化水素依存的な光合成の制御因子SqrRを起点としたパースルフィド代謝経路の解析 (2019)
  • Author(s): 清水隆之、増田建、増田真二
  • Organizer: 第10回日本光合成学会
• [Presentation] 生理活性物質としての硫化水素のシグナル伝達機構に関与するパースルフィド代謝系の解析 (2019)
  • Author(s): 清水隆之、増田建、増田真二
  • Organizer: 第60回日本植物生理学会
• [Presentation] 硫化水素依存的な光合成の制御因子SqrRはヘム応答性転写因子として機能する (2018)
  • Author(s): 清水隆之、増田建、増田真二
  • Organizer: 第9回日本光合成学会
• [Presentation] Persulfide-responsive transcriptional repressor SqrR regulates sulfide-dependent photosynthesis (2018)
  • Author(s): Takayuki Shimizu, Jiangchuan Shen, Mingxu Fang, Yixiang Zhang, Koichi Hori, Jonathan C. Trinidad, Carl E. Bauer, David P. Giedroc and Shinji Masuda
  • Organizer: 18th International Symposium of Phototrophic Prokaryotes
  • Int'l Joint Research
• [Presentation] Persulfide-responsive transcriptional repressor SqrR regulates sulfide-dependent photosynthesis (2018)
  • Author(s): Takayuki Shimizu, Jiangchuan Shen, Mingxu Fang, Yixiang Zhang, Koichi Hori, Jonathan C. Trinidad, Carl E. Bauer, David P. Giedroc and Shinji Masuda
  • Organizer: 1st Asia-Oceania International Congress on Photosynthesis
  • Int'l Joint Research