Fructose-1,6-bisphosphate promotes PI3K and glycolysis in T cells?

Trends Endocrinol Metab. 2021 Aug;32(8):540-543. doi: 10.1016/j.tem.2021.04.013. Epub 2021 May 18.

Abstract

We propose that fructose-1,6-bisphosphate (F-1,6-BP) promotes a feedback loop between phosphofructokinase-1 (PFK1), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and PFK2/PFKFB3, which enhances aerobic glycolysis and sustains effector T (Teff) cell activation, while oxidative metabolism is concomitantly downregulated. This regulation, promoted by low citrate and mitochondrial ATP synthesis, also sustains the Warburg effect in cancer cells.

Keywords: T cell; Warburg effect; cancer cell; citrate; fructose-1,6-bisphosphate; metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Citric Acid
  • Fructosediphosphates / metabolism*
  • Glycolysis*
  • Lymphocyte Activation
  • Mitochondria
  • Neoplasms
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphofructokinase-1* / genetics
  • Phosphofructokinase-1* / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • T-Lymphocytes* / metabolism

Substances

  • Fructosediphosphates
  • Citric Acid
  • Adenosine Triphosphate
  • Phosphofructokinase-1
  • Proto-Oncogene Proteins c-akt
  • fructose-1,6-diphosphate