WITHDRAWN: Parkin-mediated mitophagy ameliorates fatty acid-induced mitochondrial injury and apoptosis in tubular epithelial cells by reducing oxidative stress

Abstract

// Yue Wu 1,* , Jiangmin Wan 1,2,* , Xuemei Chen 3,* , Wei Hua 4 , Haibo Gui 3 , Xushun Jiang 1 , Huizhe Huang 5 , Xiongzhong Ruan 6,7 and Xiaogang Du 1,8 1 Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 2 Department of Nephrology, People’s Hospital of Qijiang Distract, Chongqing, China 3 Emergency Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 4 Department of Nephrology, The Sixth People’s Hospital of Chongqing, Chongqing, China 5 The second Affiliated Hospital of Chongqing Medical University, Chongqing, China 6 Centre for Nephrology, Royal Free and University College Medical School, University College London, Royal Free Campus, London, United Kingdom 7 Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China 8 The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Disease, Chongqing, China * These authors contributed equally to this work Correspondence: Xiaogang Du, email: dxgcxm@163.com Keywords : parkin; mitophagy; palmitic acid; tubular epithelial cells; apoptosis Received: October 07, 2016     Accepted: December 18, 2017     Epub: December 26, 2017 Abstract Chronic kidney disease (CKD) is often accompanied by dyslipidemia. Excessive lipid accumulation in renal tubular epithelial cells (HK-2 cells) triggers mitochondrial dysfunction and overproduction of reactive oxygen species (ROS). Mitophagy reportedly plays a crucial protective role by selectively degrading dysfunctional or damaged mitochondria. This is largely regulated by Parkin, an E3 ubiquitin ligase. In this study, we found increased Parkin, Beclin1 and LC3 expression in the renal tissues of CKD patients and rats fed a high-fat diet (HFD), and in HK-2 cells stimulated by palmitic acid (PA). We also found that PA induced upregulation and translocation of Parkin to mitochondria and increased the colocalization of Parkin and GFP-LC3 puncta, Parkin siRNA reversed this increase, indicating that Parkin participated in PA-induced mitophagy in HK-2 cells. Furthermore, our study demonstrated that PA stimulation decreased MitoTracker Red fluorescence and mitochondrial membrane potential and increased apoptosis and mitochondrial ROS generation in HK-2 cells. However, Parkin deficiency further reduced mitochondrial membrane potential, enhanced apoptosis and production of mitochondrial ROS. These data provide evidence that Parkin-mediated mitophagy plays a protective role against fatty acid-induced renal tubular epithelial cells apoptosis by reducing oxidative stress.