von Hippel-Lindau Protein Maintains Metabolic Balance to Regulate the Survival of Naive B Lymphocytes

Xu，Shengli1,2; Huo，Jianxin1; Huang，Yuhan1; Aw，Melissa1; Chen，Shuwen1; Mak，Shiya1; Yip，Lian Yee1; Ho，Ying Swan1; Ng，Sze Wai1; Tan，Andy Hee Meng1; Lee，Alison1; Ou，Xijun5; Lam，Kong Peng1,3,4

2019-07-26

10.1016/j.isci.2019.07.002

iScience   影响因子和分区

2589-0042

2589-0042

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.

Biological Sciences Cell Biology Immunology

SCI

英语

其他

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000477767700032

CELL PRESS

2-s2.0-85069635248

Scopus

1.Bioprocessing Technology InstituteAgency for ScienceTechnology and Research,Singapore,20 Biopolis Way, #06-01 Centros,138668,Singapore
2.Department of PhysiologyYong Loo Lin School of MedicineNational University of Singapore,Singapore,117559,Singapore
3.Department of Microbiology and ImmunologyYong Loo Lin School of MedicineNational University of Singapore,Singapore,117559,Singapore
4.Department of PediatricsYong Loo Lin School of MedicineNational University of Singapore,Singapore,117559,Singapore
5.Southern University of Science and Technology,Shenzhen,518055,China

Xu，Shengli,Huo，Jianxin,Huang，Yuhan,et al. von Hippel-Lindau Protein Maintains Metabolic Balance to Regulate the Survival of Naive B Lymphocytes[J]. iScience,2019,17:379-392.

Xu，Shengli.,Huo，Jianxin.,Huang，Yuhan.,Aw，Melissa.,Chen，Shuwen.,...&Lam，Kong Peng.(2019).von Hippel-Lindau Protein Maintains Metabolic Balance to Regulate the Survival of Naive B Lymphocytes.iScience,17,379-392.

Xu，Shengli,et al."von Hippel-Lindau Protein Maintains Metabolic Balance to Regulate the Survival of Naive B Lymphocytes".iScience 17(2019):379-392.