Autophagic flux defect in diabetic kidney disease results in megamitochondria formation in podocytes.
Biochem Biophys Res Commun
; 521(3): 660-667, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31679688
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.
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MEDLINE
Assunto principal:
Autofagia
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Diabetes Mellitus Experimental
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Nefropatias Diabéticas
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Podócitos
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Mitocôndrias
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article