Paraquat Exposure Induces Pulmonary Cell Mitophagy by Enhancing the PINK1/Parkin Signaling

Abstract

Paraquat (PQ) poisoning can cause oxidative stress, acute lung injury (ALI), and fibrosis. Excess oxidative stress can induce mitophagy. However, whether PQ exposure can induce mitophagy, contributing to the development of ALI and pulmonary fibrosis in vivo has not been clarified. Here, we show that PQ exposure induces ALI and fiber accumulation in the lung of rats in a time-dependent manner, accompanied by upregulating fibronectin (FN) and Collagen I (COL-I) expression. PQ exposure increased mitophagosome formation and PINK1 and Parkin expression in the lungs of rats. Similarly, PQ exposure reduced the viability and mitochondrial membrane potential, but enhanced FN, COL-I, PINK1, and Parkin expression in A549 cells. In contrast, PINK1 silencing significantly mitigated the PQ-upregulated Parkin, FN, and COL-I expression in A549 cells. Hence, PQ exposure induced ALI and fibrosis in rats by enhancing the PINK1/Parkin signaling and profibrotic factor expression in the lungs. Therefore, our findings suggest that the PINK1/Parkin signaling may be new therapeutic targets and may provide new insights in the pathogenesis of PQ-related ALI in rats.