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2020 Fiscal Year Final Research Report

Elucidation of the molecular mechanism of mitochondrial metabolism and obesity

Research Project

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Project/Area Number 18K11077
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionKyushu University

Principal Investigator

Gotoh Kazuhito  九州大学, 大学病院, 助教 (50711214)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywordsミトコンドリア / 肥満
Outline of Final Research Achievements

Dendritic cell (DC) maturation induced by Toll-like receptor agonists requires activation of downstream signal transduction and metabolic changes. Here, we demonstrate that p32/C1qbp, which functions as a multifunctional chaperone protein in mitochondria, supports mitochondrial metabolism and DC maturation. Metabolic analysis revealed that the citrate increase induced by lipopolysaccharide (LPS) is impaired in p32-deficient DCs. We also found that p32 interacts with dihydrolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase [PDH] complex) and positively regulates PDH activity in DCs. Therefore, we suggest that DC maturation is regulated by citrate production via p32-dependent PDH activity. p32-null mice administered a PDH inhibitor show decreased DC maturation and ovalbumin-specific IgG production in vivo, suggesting that p32 may serve as a therapeutic target for DC-related autoimmune diseases.

Free Research Field

臨床検査医学

Academic Significance and Societal Importance of the Research Achievements

CPI-613はマウスの卵白アルブミンを用いた卵アレルギーの病態モデルにおいて、p32部分欠損マウスと同様に卵白アルブミンに対する抗体産生量を減少させた。これらの結果により、p32やピルビン酸デヒドロゲナーゼの阻害は、卵アレルギーを含むアレルギー性疾患の創薬開発につながることが期待される。本研究は、2018年11月13日(米国東部時間)に科学誌「Cell Reports」のオンライン版で公開し、九州大学よりプレスリリースを行った。内容はオンライン誌に取り上げられ、注目を集めた。

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Published: 2022-01-27  

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