PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes
Autor: | Ting Liu, Wei Hua, Xuemei Chen, Jun-ling He, Jiang-min Wan, Xun-jia Li, Hua Gan, Xiao-Gang Du, Xu-shun Jiang |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Mitochondrial ROS Ubiquitin-Protein Ligases Palmitic Acid Biophysics Apoptosis PINK1 Mitochondrion Diet High-Fat Kidney Biochemistry Parkin Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Microscopy Electron Transmission Mitophagy Autophagy Animals Gene Silencing Obesity Molecular Biology Membrane Potential Mitochondrial Podocytes Chemistry Cell Biology Mitochondria Rats nervous system diseases Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Signal transduction Reactive Oxygen Species Microtubule-Associated Proteins Protein Kinases Signal Transduction |
Zdroj: | Biochemical and Biophysical Research Communications. 525:954-961 |
ISSN: | 0006-291X |
Popis: | 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. |
Databáze: | OpenAIRE |
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