FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis

Apoptosis. 2023 Aug;28(7-8):1128-1140. doi: 10.1007/s10495-023-01845-1. Epub 2023 Apr 29.

Abstract

Cuproptosis is a new form of programmed cell death, which is associated with the mitochondrial TCA (tricarboxylic acid) cycle. But the functions of cuproptosis in endometriosis progression are still unknown. Here, we find that cuproptosis suppresses the growth of endometriosis cells and the growth of ectopic endometrial tissues in a mouse model. FDX1 as a key regulator in cuproptosis pathway could promote cuproptosis in endometriosis cells. Interestingly, FDX1 interacts with G6PD, and reduces its protein stability, which predominantly affects the cellular redox-regulating systems. Then, the reduced G6PD activity enhances cuproptosis via down-regulating NADPH and GSH levels. Collectively, our study demonstrates that FDX1 mediates cuproptosis in endometriosis via G6PD pathway, resulting in repression of endometriosis cell proliferation and metastasis.

Keywords: Cell proliferation; Cuproptosis; Endometriosis; FDX1; G6PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Endometriosis* / genetics
  • Female
  • Ferredoxins
  • Glucosephosphate Dehydrogenase
  • Homeostasis
  • Mice
  • Oxidation-Reduction

Substances

  • Ferredoxins
  • Glucosephosphate Dehydrogenase
  • Fdx1 protein, mouse
  • G6pd protein, mouse