PINK1/Parkin-mediated mitophagy is activated to protect against testicular damage caused by aluminum

Menglin Liu; Ben Wang; Yilong Cui; Bonan Xiao; Pengli Liu; Jinsong Gao; Miao Song; Bing Shao; Yanfei Li

doi:10.1016/j.jinorgbio.2022.111840

PINK1/Parkin-mediated mitophagy is activated to protect against testicular damage caused by aluminum

J Inorg Biochem. 2022 Jul:232:111840. doi: 10.1016/j.jinorgbio.2022.111840. Epub 2022 Apr 20.

Authors

Menglin Liu¹, Ben Wang², Yilong Cui¹, Bonan Xiao¹, Pengli Liu¹, Jinsong Gao¹, Miao Song¹, Bing Shao¹, Yanfei Li³

Affiliations

¹ Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, Heilongjiang, China.
² College of Animal Science, Ji Lin Agricultural Science and Technology College, Jilin, 132101 Jilin, China.
³ Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, Heilongjiang, China. Electronic address: yanfeili_200@126.com.

PMID: 35468521
DOI: 10.1016/j.jinorgbio.2022.111840

Abstract

Oxidative stress is the main mechanism of aluminum (Al) reproductive toxicity and can also lead to mitochondrial damage. Damaged mitochondria can trigger apoptosis, leading to testicular damage. PINK1 (phosphatase and tensin homolog (PTEN)-induced putative kinase1)/Parkin (E3 ubiquitin ligase PARK2)-mediated mitophagy can remove damaged mitochondria to maintain cellular homeostasis. However, its role in testicular damage caused by Al is unclear. In this study, first, 24 male wild type (WT) C57BL/6 N mice were divided into 4 groups and orally administered with 0, 44.825, 89.65, and 179.3 mg/kg body weight AlCl₃ for 90 days, respectively. We demonstrated that apoptosis and PINK1/Parkin-mediated mitophagy were activated in a dose-effect relationship in the damaged testis caused by AlCl₃, and were most significant at 179.3 mg/kg body weight AlCl₃. Then, 40 male WT C57BL/6 N mice and 40 male Parkin knockout (Parkin^-/-) C57BL/6 N mice were divided into 4 groups and orally administered with 0, 179.3, 0 or 179.3 mg/kg body weight AlCl₃ for 90 days, respectively. Parkin^-/- inhibited mitophagy, exacerbated the growth inhibition, testicular damage, mitochondrial damage, oxidative stress, and apoptosis under AlCl₃ exposure. In general, the results reveal that AlCl₃ exposure can activate PINK1/Parkin-mediated mitophagy, and the PINK1/Parkin-mediated mitophagy plays a protective role in the testicular damage caused by AlCl₃.

Keywords: Aluminum; Apoptosis; Mitophagy; Parkin; Testicular damage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aluminum* / toxicity
Animals
Body Weight
Female
Male
Mice
Mice, Inbred C57BL
Mitophagy*
Protein Kinases
Testis
Ubiquitin-Protein Ligases

Substances

Aluminum
Ubiquitin-Protein Ligases
Protein Kinases