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Abstract: SA-PO565

Transfer of Healthy Isolated Mitochondria in Established Injury Reduces Progression to Fibrosis

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Alexander, Kyle J., University of Virginia, Charlottesville, Virginia, United States
  • Schlegel, Kailo H., University of Virginia, Charlottesville, Virginia, United States
  • Bajwa, Amandeep, University of Virginia, Charlottesville, Virginia, United States

Ischemia induces altered bioenergetics with increased mitochondrial swelling and reactive oxygen species (ROS) and ultimately degradation of cellular function. Therapeutic interventions that target to improve mitochondrial health to repair, reprogram or replace mitochondria to restore respiratory functions are beneficial for prevention and/or treatment of established disease.


Renal injury was assessed by plasma creatinine (PCr; mg/dl). 8-wk old C57BL/6 mice were i.v. injected with isolated mitochondria (50mcg, from healthy non-ischemic mouse liver). 1d, 3d or 5d after unilateral IRI. Nephrectomy of contra-lateral control kidney was done on day 13. Change in fibrosis genes were measured by RTPCR and histology changes with Masson trichrome and picrosirius red were done on day 14. For in vitro studies, PT cells (TKPTS) were treated with 10 or 20 mcg of isolated mitochondria 1d prior to analysis that included measurement of ATP levels, mitochondrial functions (Seahorse analyzer), cytokines (RTPCR), immunofluorescence microscopy (uptake efficiency) and flow cytometry (mitotracker dyes).


In vivo studies demonstrated treatment of mice with 50 mcg of mitochondria at 1d, 3d or 5d after IRI significantly protected compared to vehicle treated mice after IRI [Day 14 PCr (0.6±0.04 (+1d) vs 0.68±0.18 (+3d) vs 0.57±0.18 (+5d) vs 1.54±0.16), p<0.05]. Transfer of labeled isolated mitochondria (mitotracker dye) signal was found in spleen (in macrophages) and kidney (in PT, identified with anti-CD13 antibody [labels brush border]). The +3d mitochondria treated kidneys had significantly lower levels of Acta and Col3a1 and significantly higher PGC1α gene expression compared to vehicle treated mice at day 14. In vitro studies demonstrate that treatment of TKPTS with mitochondria had significantly higher levels of ATP, higher basal oxygen consumption rate and spare respiratory capacity measured by Seahorse analyzer.


Our current study demonstrates that up take of healthy mitochondria by PT helps maintain bioenergetics through upregulation of mitochondria biogenesis gene, PGC1α. Treatment to mice with established AKI with mitochondria attenuates progression to fibrosis compared to vehicle treated mice. Mitochondria could be used as a therapeutic modality to lessen progression of AKI to CKD.


  • Other NIH Support