2018年11月13日
Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation
Cell Reports
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- 巻
- 25
- 号
- 7
- 開始ページ
- 1800
- 終了ページ
- 1815.e4
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.celrep.2018.10.057
© 2018 The Author(s) Dendritic cell (DC) maturation induced by Toll-like receptor agonists requires activation of downstream signal transduction and metabolic changes. The endogenous metabolite citrate has recently emerged as a modulator of DC activation. However, the metabolic requirements that support citrate production remain poorly defined. 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. Although mitochondrial metabolic pathways are essential for DC activation, the precise molecular mechanism remains poorly understood. Gotoh et al. show that mitochondrial p32/C1qbp supports dendritic cell metabolism and maturation. In addition, mitochondrial p32 and pyruvate dehydrogenase activity are necessary for DC maturation in vitro and in vivo.
- リンク情報
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- DOI
- https://doi.org/10.1016/j.celrep.2018.10.057
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/30428349
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056002995&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85056002995&origin=inward
- ID情報
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- DOI : 10.1016/j.celrep.2018.10.057
- eISSN : 2211-1247
- PubMed ID : 30428349
- SCOPUS ID : 85056002995