Autophagic flux defect in diabetic kidney disease results in megamitochondria formation in podocytes
| Autor: | Chang-Yun Woo, Ranjan Kc, Ji Yeon Baek, Eun Hee Koh, Hyoun Sik Kim, Mina Kim |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Autophagosome medicine.medical_specialty Biophysics Mitochondrion Kidney Biochemistry Diabetes Mellitus Experimental Podocyte Rats Sprague-Dawley Diabetic nephropathy 03 medical and health sciences 0302 clinical medicine Internal medicine Diabetes mellitus Autophagy medicine Albuminuria Animals Diabetic Nephropathies Rats Long-Evans Molecular Biology Podocytes Chemistry Megamitochondria Cell Biology medicine.disease Angiotensin II Mitochondria Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure 030220 oncology & carcinogenesis |
| Zdroj: | Biochemical and Biophysical Research Communications. 521:660-667 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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