FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis

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. Similar content being viewed by others Data Availability The data used in this study are available from the corresponding author on reasonable request. Abbreviations - EESCs: - Ectopic endometrial stromal cells - FDX1: - ferredoxin 1 - G6PD: - glucose-6-phosphate dehydrogenease - GSH: - glutathione - NADPH: - Nicotinamide Adenine Dinucleotide Phosphate - OCR: - Oxygen Consumption Rate - PCOS: - polycystic ovary syndrome - TCA: - tricarboxylic acid - PPP: - pentose phosphate pathway - GR: - GSSG reductase - GSSG: - Oxidized glutathione

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Not Applicable. Funding The study was supported by research grants from National Natural Science Foundation of China (Grant no. 81972489 and 82003201), National Natural Science Foundation of Shandong Province (Grant no. ZR2020YQ58 and ZR2020QH255), Science and technology support plan for youth innovation in universities of Shandong Province (Grant no. 2021KJ107). Author information Authors and Affiliations Contributions J.L and X.L. conducted experiments and analyzed data. Y.S., L.L., L.L., X.W. and C.L. provided access to material and facilities and contributed reagents. C.R., X.H. and Z.Y. designed, supervised the project, and wrote the manuscript. Corresponding authors Ethics declarations Ethics approval and consent to participate In our study, all procedures performed involving were in accordance with the ethical standards of the institutional research committee of Weifang medical university. Consent for publication Not Applicable. Conflict of Interest The authors declare that they have no conflict of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Lu, J., Ling, X., Sun, Y. et al. FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis. Apoptosis 28, 1128–1140 (2023). https://doi.org/10.1007/s10495-023-01845-1 Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10495-023-01845-1