Cadmium induces mitophagy through ROS-mediated PINK1/Parkin pathway

Abstract

The results showed that Cd significantly induced MMP collapse and typical mitophagosomes formation, increased LC3-II/LC3-I ratio and PINK1 level, and decreased mitochondrial mass, revealing that Cd could induce mitophagy. However, NAC or ALC pretreatment markedly decreased Cd-induced ROS and simultaneously rescued MMP and mitochondrial mass, suggesting ROS played a crucial role in regulating mitophagy. NAC or ALC also dramatically lessened PINK1 level and mitochondrial accumulation of Parkin, indicating that ROS were related to PINK1/Parkin pathway. Notably, CsA compromised Cd-induced mitophagy, PINK1 accumulation and Parkin translocation while failed to block ROS increase, suggesting ROS functioned as an upstream signal for PINK1/Parkin pathway. Taken together, the results indicated that Cd induced ROS-mediated mitophagy through PINK1/Parkin pathway in kidneys of mice. The present study proposes a new perspective to evaluate the nephrotoxicity and its molecular mechanism under Cd exposure in vivo.