Abstract: FR-PO371
Promoting Mitochondrial Dynamics by Inhibiting the PINK1/PRKN Pathway to Relieve Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Author
- Zhu, Junyi, University of Maryland Baltimore, Baltimore, Maryland, United States
Background
Diabetes is a metabolic disorder characterized by high blood glucose levels and a leading cause of kidney disease. Dysfunctional mitochondria have been associated with diabetic nephropathy. However, many questions remain about the exact mechanism; its understanding is important to develop effective therapeutics.
Methods
Structure, function, and molecular pathways are highly conserved between mammalian podocytes and Drosophila nephrocytes Thus we used flies on a high sucrose diet to model type 2 diabetic nephropathy. We then investigated the structural and functional effects on the fly nephrocytes and their mitochondria.
Results
The nephrocytes of flies on a high sucrose diet showed remarkable levels of functional decline and decreased cell size; the flies had a shortened lifespan. Structurally, the slit diaphragm—nephrocyte filtration structure—was disorganized. At the cellular level, we found altered mitochondrial dynamics and dysfunction. Regulating mitochondrial dynamics by either genetic modification of the Pink1/Park (mammalian PINK1/PRKN) pathway or treatment with BGP-15, mitigated the mitochondrial defects and nephrocyte functional decline.
Conclusion
These findings support a role for Pink1/Park-mediated mitophagy and associated control of mitochondrial dynamics and health in diabetic nephropathy; and demonstrate that targeting this pathway might provide therapeutic benefits in type 2 diabetic nephropathy.
Funding
- Private Foundation Support