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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the U.S. Despite the rapid development of several therapies, the ability to target intrinsic kidney metabolic pathways remains somehow limited. Recently impaired mitophagy and innate immunity have been recognized as drivers of tubulointerstitial injury DKD. Our prior work discovered that glomeruli in experimental DKD exhibit sterile inflammation driven by stimulator of interferon genes (STING) activation, which results in podocyte apoptosis and autophagic death. Work from others in tubular cells showed that STING activation is triggered by mitochondrial DNA (mtDNA) release in the cytoplasm due to reduced mitochondrial transcription factor A (TFAM), a key regulator of mtDNA stability. Despite the growing evidence that mitochondrial dysfunction contributes to podocyte injury, the underlying mechanisms remain poorly defined, and therapies targeting them are lacking. We hypothesize that TFAM preserves podocyte health in DKD by maintaining PINK1- and BNIP3-mediated mitophagy and preventing mtDNA-driven inflammation.
In vitro, human podocytes with knockdown of TFAM (shTFAM) and scrambled control (shCTRL) were used to evaluate mitophagy using immunofluorescence approach and levels of cytosolic mtDNA using qRT-PCR. In vivo, we generated mice with podocyte specific Tfam deletion (pTFAMfl/fl) and induced diabetes using streptozotocin (STZ, 40 mg/kg). Diabetic db/db mice with TFAM overexpression were also generated. Mice were characterized using urinary albumin-to-creatinine ratio (ACR), histological and serum analyses. scRNA-seq analysis of the kidneys was performed using fixation and barcoding kits by Parse Biosciences. Two-tailed t-test or One-Way ANOVA followed by Tukey’s post-test were used to detect statistical changes.
We identified reduced podocyte TFAM expression in both clinical (Nephroseq data) and experimental DKD. Public snRNA-seq data further confirm reduced expression for TFAM specifically in podocytes from patients with DKD, along with decreased expression of PINK1 and BNIP3, core regulators of ubiquitin-dependent and receptor-mediated mitophagy, relatively. We also showed that podocyte TFAM deficiency leads to reduced PINK1 phosphorylation and BNIP3 expression. Furthermore, TFAM deficiency causes accumulation of mtDNA in podocyte cytosol in vitro and severe DKD progression in diabetic mice in vivo. Using scRNA-seq, we further show that diabetic TFAM deficient podocytes exhibit sterile inflammation, and downregulation of mitophagy-related genes. Global TFAM overexpression in db/db mice improves renal outcomes.
In conclusion, these findings highlight the critical role of TFAM in regulating DKD progression by targeting mitophagy-mediated quality control in podocytes.
