Kidney Week

Abstract: TH-PO056

Mitotherapy-Dependent PGC1α Activation Mitigates Mitochondrial Electron Chain Complexes Dysfunction in Cisplatin-Induced AKI

Session Information

• AKI: Epidemiology, Risk Factors, and Prevention - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

• Afjal, Mohammad Amir, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Mohammad Amir Afjal, PhD

• Stayton, Amanda Shea, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Amanda Shea Stayton

• Patel, Prisha, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Prisha Patel

• Dogan, Murat, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Murat Dogan, MD, PhD

• Watkins, Christine, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Christine Watkins

• Kuscu, Canan, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Canan Kuscu, PhD

• Kuscu, Cem, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Cem Kuscu, PhD

• Pabla, Navjot, The Ohio State University, Columbus, Ohio, United States

Navjot Pabla, PhD

• Bajwa, Amandeep, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Amandeep Bajwa, PhD

Background

Cisplatin (CP)-induced Acute kidney injury (AKI) is a significant clinical problem. While the etiology of AKI is multifactorial, evidence suggests that mitochondrial dynamics plays a critical role in its pathogenesis. Mitochondria are central to cellular energy production, and mitochondrial dysfunction decreases ATP and induces oxidative stress, apoptosis, and mitochondrial damage, all of which contribute to renal dysfunction. This study investigated the potential of mitotherapy to mitigate mitochondrial complex dysfunction in CP-induced AKI, focusing on the role of PGC1α (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) activation.

Methods

CP was used to induce AKI in male mice. Functional assessment: BUN and plasma creatinine. Histopathological: H&E). Mitochondria source: Mouse Liver (See timeline Fig1 A)

Results

Mitotherapy improve kidney function and reduced structural damage in CP-treated mice (Fig 1 B-E). Mitotherapy enhanced activation of PGC1-α and restored OXPHOS activity (Fig 1 G&F). Mitotherapy restored the balance of mitochondrial dynamics by promoting fusion (Mfn1 and Mfn2) and attenuating fission by decreased expression of Drp1 (Fig 1 H-J). These findings suggest that mitotherapy-dependent activation of PGC1-α plays a crucial role in mitigating mitochondrial complex dysfunction and protecting against cisplatin-induced AKI.

Conclusion

This study highlights the therapeutic potential of mitotherapy in enhancing mitochondrial health and offers a promising strategy for alleviating CP-induced AKI.

Fig 1