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FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis

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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.

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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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Acknowledgements

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).

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Author notes

  1. Jiayi Lu, Xi Ling and Yonghong Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, P.R. China

    Jiayi Lu, Xi Ling, Lu Liu, Lan Liu, Xiaoyun Wang, Chao Lu, Chune Ren, Xue Han & Zhenhai Yu

  2. School of Clinical Medicine, Weifang Medical University, Weifang, Shandong Province, P.R. China

    Jiayi Lu, Xi Ling, Lu Liu, Lan Liu & Xiaoyun Wang

  3. Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, P.R. China

    Yonghong Sun

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  1. Jiayi Lu
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  4. Lu Liu
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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.

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Correspondence to Chune Ren, Xue Han or Zhenhai Yu.

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In our study, all procedures performed involving were in accordance with the ethical standards of the institutional research committee of Weifang medical university.

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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

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