Sulfur-mediated energy metabolism, sulfur respiration: Its discovery and physiological functions

2023 Fiscal Year Final Research Report

• Project/Area Number: 18H05277
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section H
• Research Institution: Tohoku University
• Principal Investigator: Akaike Takaaki 東北大学, 医学系研究科, 教授 (20231798)
• Co-Investigator(Kenkyū-buntansha): 本橋 ほづみ 東北大学, 医学系研究科, 教授 (00282351) ; 西田 基宏 大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 教授 (90342641)
• Project Period (FY): 2018-06-11 – 2023-03-31
• Keywords: イオウ呼吸 / システインパースルフィド / イオウメタボローム / エネルギー代謝 / ミトコンドリア機能

Outline of Final Research Achievements

Sulfur played a crucial role in early respiration before oxygen appeared on Earth. However, its physiological functions were not well understood. Our research identified cysteinyl-tRNA synthetase as reactive persulfides synthase, which is essential for energy metabolism. Reactive persulfides, acting as electron acceptors in mitochondrial respiration, highlighted their evolutionary conservation and their role in modulating protein function and signaling pathways. Reactive persulfides (R-Sn-H/R’), abundantly synthesized in mitochondria, played a key role in redox regulation and antioxidant responses. Rich in electrons, they significantly contributed to biological processes and disease models. This study clarified sulfur's role in mammalian energy metabolism, particularly its impact on mitochondrial function and cellular energy regulation. Reactive persulfides are crucial for maintaining cellular homeostasis and could be key targets for therapeutic interventions in metabolic diseases.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

本研究における原核細胞からヒトを含めた真核・動物細胞の種横断的な活性イオウ分子の生体内生成とイオウ呼吸をはじめとする様々な活性イオウ代謝経路の発見は、タンパク質科学、ケミカルバイオロジー、レドックスバイオロジー、エネルギー代謝、分子生物学、細胞生物学、がん、老化・寿命と各種疾病の分子病態論など基礎生物学から医学・臨床科学など多彩な分野へ革新的な波及効果をもたらすことが期待される。