Kidney Week

Abstract: TH-PO0363

BNIP3 Couples Mitophagy to Extracellular Vesicle Biogenesis in Diabetic Kidney Disease

Session Information

• Glomerular Diseases: Genetics to Therapeutics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Saadat, Saeida, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, United States

Saeida Saadat, PhD

• Jarecki, Wiktor, Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Science, Gdansk, Poland

Wiktor Jarecki, MSc

• Fontanella, Antonio Miguel, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, United States

Antonio Miguel Fontanella

• Njeim, Rachel, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, United States

Rachel Njeim, PharmD, PhD

• Molina David, Judith T., Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, United States

Judith T. Molina David, PhD

• Burke, George William, Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida, United States

George William Burke, MD

• Merscher, Sandra, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, United States

Sandra Merscher, PhD

• Fornoni, Alessia, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, United States

Alessia Fornoni, MD, PhD, FASN

• Audzeyenka, Irena, Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Science, Gdansk, Poland

Irena Audzeyenka, PhD

• Mitrofanova, Alla, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, United States

Alla Mitrofanova, PhD

Group or Team Name

• Katz Family Division of Nephrology and Hypertension

Background

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the United States, and podocyte injury is central to its progression. Podocyte mitochondrial dysfunction and altered extracellular vesicle (EV) signaling are emerging drivers of glomerular injury, yet how mitochondrial quality control shapes EV biogenesis is unclear. While impaired PINK1-mediated mitophagy has been described in DKD, the role of receptor-mediated mitophagy via BNIP3 in podocytes remains unknown. We hypothesized that BNIP3 links mitophagy and EV biogenesis in podocytes under diabetic stress.

Methods

Glomeruli from diabetic db/db and non-diabetic mice were analyzed for mitochondrial abnormalities, mitophagy signaling, and podocyte injury. Cultured podocytes exposed to high glucose modeled diabetic stress, and EVs were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and EV marker expression. BNIP3 expression was further assessed in human biopsies and using public glomerular transcriptomic datasets (KIT, KPMP).

Results

Diabetic db/db mice demonstrated mitochondrial abnormalities, impaired mitophagy, and reduced BNIP3 expression in glomeruli. Immunoperoxidase staining of kidney sections from patients with diabetes showed decreased BNIP3 expression. High-glucose-treated podocytes released larger EVs enriched in mitochondrial DNA, linking mitochondrial dysfunction and deficient mitophagy to altered EV cargo.

Conclusion

These findings identify an association of BNIP3-dependent mitophagy and EV biogenesis in diabetic podocytes and reveal a novel connection between mitochondrial dysfunction and EV-mediated signaling in DKD. Targeting this pathway may be considered to slow DKD progression.

Acknowledgment

A.M. and G.W.B. are supported by Chernowitz Medical Research Foundation GR021608. A.M. is supported by Carl W. Gottschalk Research Scholar Grant, American Society of Nephrology GR018262, Career Development Award, American Heart Association 24CDA1267060 and by the Miami Clinical and Translational Science Institute, Grant Number UL1TR002736, from the National Center for Advancing Translational Sciences. AIA and WJ are supported by National Science Centre NCN, 202351BNZ500885 Poland

Funding

• Private Foundation Support