Quercetin Attenuates Palmitate-Induced MIN6 Cell Injury via Activation of PINK1/Parkin-Mediated Mitophagy

Abstract Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder worldwide. Insulin resistance and islet β-cell dysfunction are major contributing factors. Quercetin is a natural compound has anti-inflammatory and antioxidant effects. This study aimed to explore the effects and mechanisms of quercetin in palmitic acid (PA)-induced islet β-cell line MIN6 cell damage and focused on the role of quercetin in mitophagy mediated by PINK1/Parkin. We used flow cytometry to analyze apoptosis and reactive oxygen species (ROS) production rate. Mitochondrial-lysosomal colocalization and mitochondrial membrane potential (ΔΨm) were detected using fluorescence microscopy and flow cytometry. Protein level of Bax, PINK1, Parkin, p62 and Bcl-2 were detected using Western Blot. ATP levels were measured using a luminescence-based assay kit. Oxygen consumption rate (OCR) was detected via the Seahorse XF24 Analyzer. Results showed that PA promoted the apoptosis of MIN6 cells, inhibited PINK1-dependent mitophagy, enhanced the ROS production rate and reduced the ATP content, ΔΨm and OCR. Quercetin significantly inhibited apoptosis and enhanced PINK1-dependent mitophagy, reduced the ROS production rate, enhanced ATP, ΔΨm and OCR. These protective effects of quercetin were partially reversed by the inhibition of mitophagy. In conclusion, quercetin alleviates MIN6 cell injury partially by the activation of PINK1/Parkin-mediated mitophagy.