CISD2 regulates oxidative stress and mitophagy to maintain the balance of the follicular microenvironment in PCOS

Objectives: To observe the CISD2 expression among PCOS patients and to explore its profound impact on the follicular microenvironment. Moreover, we want to elucidate the intricate mechanistic contribution of CISD2 to the onset and progression of PCOS.

Methods: Oxidase NOX2, mitophagy-related proteins, and CISD2 were detected by WB. The changes in mitochondrial structure and quantity were observed by transmission electron microscopy. Mitochondrial and lysosome colocalization was used to detect the changes of Mitophagy. MDA kit, GSH and GSSG Assay kit and ROS probe were used to detect oxidative stress damage.

Results: We found that CISD2, Mitophagy and oxidase in the GCs of PCOS patients were significantly increased. Testosterone stimulation leads to the increase of oxidase, Mitophagy, and CISD2 in KGN cells. CISD2 inhibition promoted the increase of Mitophagy, and the activation of mitochondria-lysosome binding, while alleviating the oxidative stress.

Conclusions: Inhibition of CISD2 can improve the occurrence of oxidative stress by increasing the level of Mitophagy, thus affecting the occurrence and development of PCOS diseases.

CDGSH iron sulfur domain 2; hyperandrogenemia; mitophagy; oxidative stress; polycystic ovary syndrome.