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.

铜中毒是一种新形式的程序性细胞死亡，与线粒体 TCA（三羧酸）循环有关。但铜凋亡在子宫内膜异位症进展中的作用仍不清楚。在这里，我们发现铜凋亡抑制小鼠模型中子宫内膜异位细胞的生长和异位子宫内膜组织的生长。 FDX1作为铜凋亡途径的关键调节因子可以促进子宫内膜异位细胞的铜凋亡。有趣的是，FDX1 与 G6PD 相互作用，并降低其蛋白质稳定性，这主要影响细胞氧化还原调节系统。然后，G6PD 活性的降低通过下调 NADPH 和 GSH 水平来增强铜凋亡。总的来说，我们的研究表明，FDX1 通过 G6PD 途径介导子宫内膜异位症的铜凋亡，从而抑制子宫内膜异位症细胞的增殖和转移。