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

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.

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