Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells.

Zinc (Zn) is a critical microelement for physiological process, but excess exposure can cause testicular dysfunction. However, the underlying mechanism of Zn-induced ferroptosis via regulating mitophagy is unknown. In this study, a total of 60 male weaned pigs were randomly divided into three groups and the content of Zn were 75 mg/kg (control), 750 mg/kg (Zn-I), 1500 mg/kg (Zn-II). Meanwhile, testicular cells were treated with ZnSO4 (0, 50 and 100 μM), and in combination of ZnSO4 (100 μM) and ferrostation-1, ML-210, or 3-methyladenine for 24 h. Our results verified that Zn could cause ferroptosis and lipid peroxidation, which were characterized by down-regulating level of SLC7A11, GPX4, and ferritin, and up-regulating levels of MDA, CD71, TF, and HMGB1 by Western blot, immunohistochemistry, immunofluorescence, peroxidase assay, et.ac. The opposite effect was shown after treatment with ferrostation-1 or ML-210. Meanwhile, the mitophagy-related proteins (PINK, Parkin, ATG5, LC3-II/LC3-I) were significantly upregulated in vivo and in vitro. Most importantly, 3-methyladenine observably relieved ferroptosis under Zn treatment through inhibiting mitophagy. Collectively, we demonstrated that mitophagy contributes to Zn-induced ferroptosis in porcine testis cells, providing a new insight into Zn toxicology. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Quanwei Li, Qingwen Yang, Pan Guo, Yuanhong Feng, Shaofeng Wang, Jianying Guo, Zhaoxin Tang, Wenlan Yu, Jianzhao Liao. Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2023 Sep;179:113950

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PMID: 37481227

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