PINK1/Parkin-Mediated Mitophagy Plays a Protective Role in Albumin Overload-Induced Renal Tubular Cell Injury

Background: Proteinuria is an important symptom of chronic kidney disease irrespective of its initial pathogenesis. Mitochondrial dysfunction is an early pathophysiological event in proteinuria-induced tubular damage. Mitophagy, the selective degradation of damaged mitochondria targeted by autophagy, contributes to mitochondrial homeostasis and is primarily regulated by the PTEN-induced kinase 1 (PINK1)/Parkin pathway. In this study, we evaluated the function of mitophagy in proteinuria-induced tubular injury and mechanism. Methods: HK-2 cells were transfected with Parkin siRNA or Parkin overexpression plasmids for 48 h followed by treatment with albumin (8 mg/mL) for 8 h. JC-1 staining, ATP detection, and reactive oxygen species (ROS) detection were used to determine mitochondrial function. Immunoblot, LC3/mitochondria co-localization analyses, and Mito-Keima were employed to detect mitophagy. Immunoblot analysis and TUNEL were used to detect apoptosis. Results: Albumin overload induced mitochondrial dysfunction and mitophagy activation in HK-2 cells. Parkin knockdown inhibited albumin overload induced-mitophagy. Parkin overexpression further upregulated albumin overload induced-mitophagy. Parkin deficiency aggravated albumin overload-induced mitochondrial dysfunction and the overproduction of ROS, resulting in increased cell injury. Contrarily, Parkin overexpression helped maintain mitochondrial function and attenuate ROS generation, contributing to cell protection. Conclusions: Our results suggest that by clearing damaged mitochondria and maintaining mitochondrial function, PINK1/Parkin-mediated mitophagy contributed to tubular cell survival during albumin overload. PINK1/Parkin-mediated mitophagy may be a potential therapeutic target for proteinuria in tubular epithelial cells.