Summary
B lymphocytes undergo metabolic reprogramming upon activation to meet the bioenergetic demands for proliferation and differentiation. Yet, little is known if and how the fate of naive B cells is metabolically regulated. Here, we specifically delete von Hippel-Lindau protein (VHL) in B cells using CD19-Cre and demonstrate that metabolic balance is essential for naive B cell survival. Loss of VHL disturbs glycolytic and oxidative metabolic balance and causes severe reduction in mature B cells. Mechanistically, the metabolic imbalance in VHL-deficient B cells, arising from over-stabilization of hypoxia-inducible factor-1α (HIF-1α), triggers reductive glutamine metabolism leading to increased Fas palmitoylation and caspase-8-mediated apoptosis. Blockade of reductive glutamine metabolic flux by lactate supplementation and ATP citrate lyase inhibition restores the metabolic balance and rectifies the impaired survival of VHL-deficient B cells. Hence, we unravel that the VHL/HIF-1α pathway is required to maintain the metabolic balance of naive B cells and ensure their survival.
Thioethers Q 0580Copper-Catalyzed Ullman Coupling under Ligand-and Additive-Free Conditions. Part 2. S-Arylation of Thiols with Aryl Iodides. -The yields are generally good to excellent for aryl thiols under conditions A). In the case of aliphatic substrate (IV), the moderate yield can be increased by changing the base and the solvent. -(BURANAPRASERTSUK, P.; CHANG,
Phenol ethers Q 0270Copper-Catalyzed Ullmann Coupling under Ligand-and Additive-Free Conditions. Part 1. O-Arylation of Phenols with Aryl Halides. -A practical procedure for the Ullmann-type etherification of aryl iodides is developed using a mixture of CuI and Bu4NBr. The process can be applied to a broad spectrum of phenols. Aliphatic alcohols can also be used; however, the results are dependent on the conditions in the case of substrates (IVb) and (VII). -(CHANG,
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