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Title: von Hippel-Lindau Protein Maintains Metabolic Balance to Regulate the Survival of Naive B Lymphocytes
Authors: Xu, S. 
Huo, J.
Huang, Y.
Aw, M.
Chen, S.
Mak, S.
Yip, L.Y.
Ho, Y.S.
Ng, S.W.
Tan, A.H.-M.
Lee, A.
Ou, X.
Lam, K.-P. 
Keywords: Biological Sciences
Cell Biology
Issue Date: 2019
Publisher: Elsevier Inc.
Citation: Xu, S., Huo, J., Huang, Y., Aw, M., Chen, S., Mak, S., Yip, L.Y., Ho, Y.S., Ng, S.W., Tan, A.H.-M., Lee, A., Ou, X., Lam, K.-P. (2019). von Hippel-Lindau Protein Maintains Metabolic Balance to Regulate the Survival of Naive B Lymphocytes. iScience 17 : 379-392. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: 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-1? (HIF-1?), 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-1? pathway is required to maintain the metabolic balance of naive B cells and ensure their survival. © 2019 The Author(s)Biological Sciences; Immunology; Cell Biology © 2019 The Author(s)
Source Title: iScience
ISSN: 25890042
DOI: 10.1016/j.isci.2019.07.002
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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