PI3K-dependent reprogramming of hexokinase isoforms controls glucose metabolism and functional responses of B lymphocytes.

ABSTRACT: B lymphocyte activation triggers metabolic reprogramming essential for B cell differentiation and mounting a healthy immune response. Here, we investigate the regulation and function of glucose-phosphorylating enzyme hexokinase 2 (HK2) in B cells. We report that both activation-dependent expression and mitochondrial localization of HK2 are regulated by the phosphatidylinositol 3-kinase (PI3K) signaling pathway. B cell-specific deletion of HK2 in mice caused mild perturbations in B cell development. HK2-deficient B cells show impaired functional responses in vitro and adapt to become less dependent on glucose and more dependent on glutamine. HK2 deficiency impairs glycolysis, alters metabolite profiles, and alters flux of labeled glucose carbons into downstream pathways. Upon immuniz

SUBMITTER: Paradoski BT 

PROVIDER: S-EPMC11615188 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature