Selenium alleviates cadmium-induced mitophagy through FUNDC1-mediated mitochondrial quality control pathway in the lungs of sheep

Cadmium (Cd) is a poisonous metal element that causes mitochondrial dysfunction. Selenium (Se) can reduce the damage of Cd to various organs of animals, but the protective mechanism of Se in Cd-induced lung injury has not been fully elucidated. For purpose of further illustrating the specific mechanism of Se alleviated Cd-triggered pulmonary toxicity, 48 sheep were divided into 4 groups, of which the sheep in the treatment group were taken 1 mg/kg body weight (BW) of Cd, 0.34 mg/kg BW of Se, and 0.34 mg Se + 1 mg/kg BW of Cd by intragastric administration for 50 d, respectively. The results indicated that Cd caused inflammatory cell infiltration and alveolar wall thickening, which facilitated mitochondrial vacuolation and formation of mitophagosomes in lung tissues. Simultaneously, Cd treatment impaired the antioxidant capacity of sheep lung tissue. Additionally, Cd treatment down-regulated the expression levels of mitochondrial biogenesis and mitochondrial fusion, but up-regulated the levels of mitochondrial fission and mitophagy mediated by FUNDC1. Moreover, the immunofluorescence co-localization puncta of LC3B/COX IV, LC3B/FUNDC1 were increased after Cd treatment. Nevertheless, co-treatment with Se improved effectively the above variation caused by Cd exposure. In summary, Se could mitigate Cd-generated mitophagy through FUNDC1-mediated mitochondrial quality control pathway in the lungs of sheep.