Autophagic flux defect in diabetic kidney disease results in megamitochondria formation in podocytes |
| |
Affiliation: | 1. Dept. of Nephrology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;2. Dept. of Diabetes and Metabolic Diseases, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;3. Dept. of Pharmacology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;4. Dept. of Cellular and Molecular Biology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;5. Dept. of Public Health Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;6. Dept. of Neurology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;7. Dept. of Anatomy and Embryology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;8. Nefrotim Medical Center, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;9. Centre of Translational Research and Systems Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania;10. “Victor Babes” University of Medicine and Pharmacy Timisoara, Romania |
| |
Abstract: | Podocyte injury is an important factor in the pathogenesis of diabetic nephropathy. Podocytes are characterized by large numbers of mitochondria. However, mitochondrial dysfunction as it relates to kidney pathology remains poorly understood. The present study found that podocyte mitochondria in different animal models of diabetes mellitus became elongated with the development of albuminuria, suggesting a change in mitochondrial dynamics. We then treated cells with a combination of glucose, fatty acids, and angiotensin II (GFA) to mimic the diabetic milieu. Cultured podocytes exposed to GFA showed megamitochondria formation and decreased autophagosome degradation. We also found that GFA treatment decreased the binding of the autophagosome to the lysosome. Our results suggest that megamitochondria are common in podocytes during diabetic nephropathy and that insufficient autophagy flux may underlie this effect. These findings have expanded our understanding of the pathogenesis of diabetic nephropathy and identified a potential pharmacological target for treatment. |
| |
Keywords: | Diabetic nephropathy Podocyte Megamitochondria Autophagy Mitochondria |
本文献已被 ScienceDirect 等数据库收录! |
|