New mechanism of metformin action mediated by lysosomal presenilin enhancer 2

J Diabetes Investig. 2023 Jan;14(1):12-14. doi: 10.1111/jdi.13925. Epub 2022 Oct 28.

Abstract

Formation of the PEN2-ATP6AP1 complex induced by the binding of metformin to PEN2 results in the inhibition of v-ATPase activity and in the recruitment of AXIN/LKB1 to lysosomes, which in turn results in the phosphorylation and activation of AMPK.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Humans
  • Lysosomes / metabolism
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Presenilins / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Vacuolar Proton-Translocating ATPases* / metabolism

Substances

  • Metformin
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Presenilins
  • ATP6AP1 protein, human
  • Vacuolar Proton-Translocating ATPases