Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation
| Autor: | Kazuhito Gotoh, Takafumi Morisaki, Daiki Setoyama, Katsuhiko Sasaki, Mikako Yagi, Ko Igami, Soichi Mizuguchi, Takeshi Uchiumi, Yoshinori Fukui, Dongchon Kang |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Cell Reports, Vol 25, Iss 7, Pp 1800-1815.e4 (2018) |
| Druh dokumentu: | article |
| ISSN: | 2211-1247 82345872 |
| DOI: | 10.1016/j.celrep.2018.10.057 |
| Popis: | Summary: 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. Keywords: dendritic cell, mitochondria, p32/C1qbp, citrate, pyruvate dehydrogenase |
| Databáze: | Directory of Open Access Journals |
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