ROS antagonizes the protection of Parkin-mediated mitophagy against aluminum-induced liver inflammatory injury in mice.

Aluminum (Al) is a food pollutant that has extensive deleterious effects on the liver. Our previous research proposed that E3 ubiquitin ligase PARK2 knockout (Parkin−/-) could aggravate Al-induced liver damage by inhibiting mitophagy, during which the reactive oxygen species (ROS) content increases. Inhibition of mitophagy can activate inflammasome. But the link between Parkin-mediated mitophagy and liver inflammatory injury caused by Al, and the role of ROS in it remain unclear. In this study, we applied Al, Parkin−/- and N-acetyl-L-cysteine (NAC) to act on C57BL/6N mice to investigate them. We found that Al could induce liver inflammatory injury and Parkin−/- could aggravate it. Meanwhile, inhibition of ROS alleviated oxidative stress, mitochondrial damage, mitophagy and inflammatory injury caused by Al in Parkin−/- mice liver. These results indicated that ROS antagonized the protection of Parkin-mediated mitophagy against Al-induced liver inflammatory damage in mice. [Display omitted] • Parkin−/- aggravates Al-induced liver inflammatory injury. • Inhibition of ROS suppresses Al-induced oxidative stress in Parkin−/- mice. • Inhibition of ROS alleviates Al-induced mitochondrial damage in Parkin−/- mice. • Inhibition of ROS down-regulates Al-induced mitophagy level in Parkin−/- mice. • Inhibition of ROS attenuates Al-induced inflammatory injury in Parkin−/- mice. [ABSTRACT FROM AUTHOR]