PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes

• Published in: Biochemical and biophysical research communications 2020-05, Vol.525 (4), p.954-961
• Main Authors: Jiang, Xu-shun, Chen, Xue-mei, Hua, Wei, He, Jun-ling, Liu, Ting, Li, Xun-jia, Wan, Jiang-min, Gan, Hua, Du, Xiao-gang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Autophagy - drug effects; Autophagy - genetics; Diet, High-Fat; Gene Silencing; Kidney - metabolism; Kidney - physiopathology; Male; Membrane Potential, Mitochondrial - physiology; Microscopy, Electron, Transmission; Microtubule-Associated Proteins - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - ultrastructure; Mitophagy; Mitophagy - genetics; Obesity - metabolism; Palmitic acid; Palmitic Acid - pharmacology; PINK1/Parkin; Podocytes; Podocytes - drug effects; Podocytes - metabolism; Podocytes - ultrastructure; Protein Kinases - genetics; Protein Kinases - metabolism; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Signal Transduction - genetics; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.02.170

Diabetic nephropathy (DN), the primary cause of end-stage renal disease (ESRD), is often accompanied by dyslipidemia, which is closely related to the occurrence and development of DN and even the progression to ESRD. Mitophagy, the selective degradation of damaged and dysfunctional mitochondria by autophagy, is a crucial mitochondrial quality control mechanism, and largely regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin signaling pathway. In the present study, we demonstrated that PA induced mitochondrial damage and excessive mitoROS generation in podocytes. We also found PA treatment resulted in the activation of mitophagy by increasing co-localization of GFP-LC3 with mitochondria and enhancing the formation of mitophagosome, stabilization of PINK1 and mitochondrial translocation of Parkin, which indicated that PINK1/Parkin pathway was involved in PA-induced mitophagy in podocytes. Furthermore, inhibition of mitophagy by silencing Parkin dramatically aggravated PA-induced mitochondrial dysfunction, mitoROS production, and further enhanced PA-induced apoptosis of podocytes. Finally, we showed that PINK1/Parkin pathway were up-regulated in kidney of high fat diet (HFD)-induced obese rats. Taken together, our results suggest that PINK1/Parkin mediated mitophagy plays a protective role in PA-induced podocytes apoptosis through reducing mitochondrial ROS production and that enhancing mitophagy provides a potential therapeutic strategy for kidney diseases with hyperlipidemia, such as DN. •PA induced lipotoxicity promoted podocytes injury and apoptosis.•PA induced mitochondrial injury, a decreased ΔΨm and excessive mitoROS generation in podocytes.•PINK1/Parkin pathway was involved in PA-induced mitophagy in podocytes.•PINK1/Parkin mediated mitophagy play a protective role in PA-induced apoptosis of podocytes by reducing mitoROS production.