2. Academic Validation
  3. Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells

Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells

  • Food Chem Toxicol. 2023 Jul 20;113950. doi: 10.1016/j.fct.2023.113950.
Quanwei Li 1,  Qingwen Yang 2,  Pan Guo 1,  Yuanhong Feng 1,  Shaofeng Wang 1,  Jianying Guo 1,  Zhaoxin Tang 1,  Wenlan Yu 3,  Jianzhao Liao 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China.
  • 2 Laboratory of Veterinary Pharmacology, Department of Animal Science and Technology, Chongqing Three Gorges Vocational College, Chongqing, PR China.
  • 3 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China. Electronic address: [email protected].
  • 4 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China. Electronic address: [email protected].
PMID: 37481227 DOI: 10.1016/j.fct.2023.113950
Abstract

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.

Keywords

Ferroptosis; Mitophagy; Reproduction toxicity; Testicular cells; Zinc.

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