| First Author | Gotoh K | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 7 | Pages | 1800-1815.e4 |
| PubMed ID | 30428349 | Mgi Jnum | J:270860 |
| Mgi Id | MGI:6278804 | Doi | 10.1016/j.celrep.2018.10.057 |
| Citation | Gotoh K, et al. (2018) Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation. Cell Rep 25(7):1800-1815.e4 |
| abstractText | 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. |
