Abstract: FR-PO169

Metabolic Syndrome Induces Transit Peptide Protein Import into the Mitochondria of Porcine Mesenchymal Stem Cells

Session Information

  • Mitochondriacs and More
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress

Authors

  • Aghajani nargesi, Arash, Mayo Clinic, Rochester, Minnesota, United States
  • Hickson, LaTonya J., Mayo Clinic, Rochester, Minnesota, United States
  • Jordan, Kyra L., Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States
Background

Autologous transplantation of mesenchymal stem cells (MSC) is currently being tested in clinical trials for patients with renal disease. Mitochondrial aerobic respiration is essential for successful differentiation of MSC, but whether coexisting cardiovascular risk factors modulate MSC mitochondrial function remains unknown. We hypothesized that metabolic syndrome (MetS) alters expression of genes regulating mitochondrial biogenesis and metabolism.

Methods

MSC were isolated from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet (n=5 each). Next-generation sequencing was performed to detect differentially expressed mRNA in MetS-MSC, and mitochondrial genes were identified (MitoCarta). Expression of the mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α was measured by western blot. Finally, we assessed protein expression of transporters of mitochondrial transit peptides (MTP), including translocase of outer membrane (TOMM)-34, heat shock protein (HSP)-70, and HSP90.

Results

Out of 1,088 unique mitochondrial mRNA, 45 were upregulated in MetS- vs. Lean-MSC (fold change >1.4, p<0.05), of which MTP, primarily involved in oxidative phosphorylation and electron transport, comprised the top category. Protein expression of PGC-1α, TOMM34, HSP70, and HSP90 was upregulated in MetS-MSC.

Conclusion

MetS upregulates MSC mRNA expression of MTP, and protein expression of mitochondrial membrane transporters that import them into mitochondria. These might be linked to altered mitochondrial biogenesis and may impact aerobic metabolism. These observations provide a molecular framework for optimization of cell-based strategies as we move towards clinical applications of MSC for renal repair.

Funding

  • NIDDK Support