Analysis about mitochondrial genome signaling for activating NLRP3 inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20640
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Kasho Kazutoshi 九州大学, 薬学研究院, 助教 (90726019)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: ミトコンドリア / mtDNA / 複製 / NLRP3

Outline of Final Research Achievements

Mitochondrial genome (mtDNA) is an essential signaling factor for the activation of the NLRP3 inflammasome against a broad range of pathogens such as LPS (lipopolysaccharides) and in response, activates inflammation. Mitochondria are able to sense an innate immune priming event caused by an injury or a microbial damage, and convert this signal via mtDNA release to activate NLRP3, which occurs through LPS-dependent increase of mtDNA copy number and subsequent mtDNA modification. However, the mechanism for stimulating mtDNA replication remains unveiled. This study tried to reveal the regulatory mechanism for mtDNA copy number after LPS treatment and to reconstitute mtDNA replication in vitro.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究はNLRP3炎症反応の起点となるLPS依存的mtDNA複製における複製モードとその制御様式の解明を目指す初の試みであり新規性、独自性が高い。加えて、NLRP3炎症反応の制御因子としてmtDNA複製促進に必須な因子を探索するというアプローチも独創的と言える。本研究を基盤にして新規NLRP3制御因子が同定されれば、神経変性疾患などの炎症過剰亢進に起因する疾患の治療薬ターゲットの創造に繋がる。