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.

ROS act as an upstream signal to mediate cadmium-induced mitophagy in mouse brain

“…Recent studies have suggested that Cd can induce mitophagy in mouse kidney and liver cells (Pi et al, 2013;Wei et al, 2014). Our data showed that Cd also could induce mitophagy in mouse brain.…”

“…ROS can damage mitochondria and are typically associated with mitophagy in yeast and mouse kidney (Kurihara et al, 2012;Wei et al, 2014). The present study also suggested that Cd induced excess ROS production and addressed the role of ROS in Cdinduced mitophagy in mouse brain.…”

“…Eventually, mitophagy removes damaged mitochondria by regulating mitochondrial mass (Park et al, 2012) and number (Youle and Narendra, 2010). Recent studies have showed that cadmium (Cd) can induce mitophagy in mouse kidney and liver cells (Pi et al, 2013;Wei et al, 2014). However, the impact of Cd on mitophagy in mouse brain and its molecular mechanism have not been explored.…”

Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury

“…Other studies have demonstrated that ROS plays a crucial role in regulating mitophagy. Cadmium induced ROS-mediated mitophagy through PINK1/Parkin pathway in kidneys of mice [35, 36]. However, the effects of IOCM and LOCM on mitochondrial ROS generation and mitochondrial damage still remain unclear.…”

The mitochondrial dynamics in cancer and immune-surveillance

“…Defective removal of damaged mitochondria could lead to increased ROS amounts with consequent accumulation of mutations in mitochondrial and nuclear DNA, thus favouring cancer onset. Mitophagy has been implicated in the removal of damaged mitochondria containing high levels of ROS [136,137] and ROS accumulation can promote by itself mitophagy activation, for example through mitochondrial membrane depolarization and Parkin/PINK1 pathway activation [138,139], thereby inhibiting initial tumor growth. Indeed, Parkin deficient mice spontaneously develop hepatic tumors [140], and PINK1 mutations have been described in neuroblastoma [141].…”