2019 Fiscal Year Final Research Report

Signal transduction by redox sensor molecules

Planned Research

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Project Area	Oxygen biology: a new criterion for integrated understanding of life
Project/Area Number	26111007
Research Category	Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Allocation Type	Single-year Grants
Review Section	Biological Sciences
Research Institution	Osaka University
Principal Investigator	Miki Hiroaki 大阪大学, 微生物病研究所, 教授 (80302602)
Co-Investigator(Kenkyū-buntansha)	藤澤貴央東京大学, 大学院薬学系研究科(薬学部), 助教 (50636644) 服部一輝東京大学, 大学院薬学系研究科(薬学部), 助教 (40708575) 関根史織東京大学, 薬学研究科(研究院), 助教 (70612654)
Project Period (FY)	2014-07-10 – 2019-03-31
Keywords	シグナル伝達 / ストレス
Outline of Final Research Achievements	(1) We performed functional analyses of PRL, a redox sensor molecule. We found a novel regulatory mechanism of the complex formation with its target molecule CNNM and a unique role in the regulation of energy metabolism and blood pressure. (2) We also performed functional analyses of another redox sensor molecule KLHDC10. We found its involvement in systemic inflammation by promoting cell death and the importance of ASK1, which functions downstream of KLHDC10, in cell death induced by the accumulation of peroxidized lipids, which is called ferroptosis.
Free Research Field	細胞生物学
Academic Significance and Societal Importance of the Research Achievements	活性酸素は酸素呼吸に伴って生じる毒物的なものとして認識されてきたが、生物はそれを積極的に利用して生命機能の調節に役立てている。本研究では、この活性酸素に応答して適切な細胞応答を起こすレドックセンサー分子にフォーカスして解析を進めた。その結果、各レドックスセンサー分子の機能調節の仕組みや、血圧調節・炎症制御などヒト疾患にも密接に関わるマクロな現象との関連も明らかにできた。