PINK1/Parkin-Mediated Mitophagy Plays a Protective Role in the Bone Impairment Caused by Aluminum Exposure.

ABSTRACT

The pollution of aluminum (Al) in agricultural production and its wide application in food processing greatly increase the chance of human and animal exposure. Al can accumulate in bone and cause bone diseases by inducing oxidative stress. Mitophagy can maintain normal cell function by degrading damaged mitochondria and scavenging reactive oxygen species. However, the role of mitophagy in the bone impairment caused by Al is unknown. In this study, we demonstrated that PTEN induced putative kinase 1 (PINK1)/ E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy was activated in the bone impairment caused by Al in vivo. Then, the Al-induced mitophagy in Parkin-deficient mice and MC3T3-E1 cells were decreased. Meanwhile, Parkin deficiency exacerbated the bone impairment, mitochondrial damage, and oxidative stress under Al exposure, both in vivo and in vitro. In general, the results reveal that Al exposure can activate PINK1/Parkin-mediated mitophagy, and the PINK1/Parkin-mediated mitophagy plays a protective role in the bone impairment caused by Al.