Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation

Kazuhito Gotoh, Takafumi Morisaki, Daiki Setoyama, Katsuhiko Sasaki, Mikako Yagi, Ko Igami, Soichi Mizuguchi, Takeshi Uchiumi, Yoshinori Fukui, Dongchon Kang

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)1800-1815.e4
ジャーナルCell Reports
25
発行部数7
DOI
出版物ステータス出版済み - 11 13 2018

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Metabolism
Dendritic Cells
Pyruvic Acid
Citric Acid
Oxidoreductases
Dihydrolipoyllysine-Residue Acetyltransferase
Chemical activation
Pyruvate Dehydrogenase Complex
Signal transduction
Mitochondria
Toll-Like Receptors
Ovalbumin
Metabolites
Metabolic Networks and Pathways
Modulators
Autoimmune Diseases
Lipopolysaccharides
Signal Transduction
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation. / Gotoh, Kazuhito; Morisaki, Takafumi; Setoyama, Daiki; Sasaki, Katsuhiko; Yagi, Mikako; Igami, Ko; Mizuguchi, Soichi; Uchiumi, Takeshi; Fukui, Yoshinori; Kang, Dongchon.

:: Cell Reports, 巻 25, 番号 7, 13.11.2018, p. 1800-1815.e4.

研究成果: ジャーナルへの寄稿記事

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abstract = "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.",
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AU - Gotoh, Kazuhito

AU - Morisaki, Takafumi

AU - Setoyama, Daiki

AU - Sasaki, Katsuhiko

AU - Yagi, Mikako

AU - Igami, Ko

AU - Mizuguchi, Soichi

AU - Uchiumi, Takeshi

AU - Fukui, Yoshinori

AU - Kang, Dongchon

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