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

PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes. Biochem Biophys Res Commun. 2020 Mar 12;: Authors: Jiang XS, Chen XM, Hua W, He JL, Liu T, Li XJ, Wan JM, Gan H, Du XG Abstract 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 (...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research