PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells

Abstract

Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides. There are links between CPF exposure and neurological disorders. Mitochondrial damage has been implicated to play a key role in CPF-induced neurotoxicity. Mitophagy, the selective autophagic elimination of mitochondria, is an important mitochondrial quality control mechanism. However, the role of mitophagy in CPF-induced neurotoxicity remains unclear. In this study, CPF-caused mitochondrial damage, role and mechanism of mitophagy on CPF-induced neuroapoptosis were extensively studied by using SH-SY5Y cells. We showed that CPF treatment caused mitochondrial fragmentation, excessive ROS generation and mitochondrial depolarization, thus led to cell apoptosis. Moreover, CPF treatment also resulted in increased colocalizaton of mitochondria with LC3, decreased levels of mitochondrial proteins, PINK1 stabilization and mitochondrial accumulation of Parkin. These data suggested that CPF treatment induced PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Furthermore, knockdown of Parkin dramatically increased CPF-induced neuroapoptosis. On the other hand, overexpression of Parkin markedly alleviated CPF-induced SH-SY5Y cell apoptosis. Together, these findings implicate a protective role of PINK1/Parkin-mediated mitophagy against neuroapoptosis and that enhancing mitophagy provides a potential therapeutic strategy for CPF-induced neurological disorders.

Mechanism underlying the effect of long‐term exposure to low dose of pesticides on DNA integrity

“…Impaired mitochondria were found in CPF‐treated neuronal cells. The CPF exposure induced mitophagy, which was cytoprotective for CPF‐induced apoptosis in SHSY‐5Y cells . The altered mitochondrial dysfunction was associated with ROS generation in both cell lines (cf Figure ).…”

Organic honey supplementation reverses pesticide‐induced genotoxicity by modulating DNA damage response

“…Conversely, CPF decreased cell proliferation in a dose‐dependent manner in both cell lines. Mitochondrial damage has been implicated to play a key role in pesticide‐induced neurotoxicity . We showed that GLY and CPF treatment caused increased mitochondrial activity at low doses, while inhibiting mitochondrial activity at higher concentrations.…”

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

“…However, in both European Society of Urogenital Radiology and the Kidney Disease: Improving Global Outcomes guidelines, either IOCM or LOCM was recommended in patients with increased risk of CI-AKI [28, 29]. Mounting evidence demonstrated that ROS generation and mitochondrial membrane depolarization may lead to DNA damage and apoptosis [30, 31]. Recent studies indicated that an excess generation of mitochondrial ROS played an important role in the pathogenesis of AKI [32, 33].…”