Abstract: FR-PO160

Sulfotransferase 1C2 (SULT1C2) Post-Translationally Increases Mitochondria Respiration

Session Information

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

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Kolb, Alexander Louis, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Pfaffenberger, Zechariah, Indiana Wesleyan University, Mishawaka, Indiana, United States
  • Winfree, Seth, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Atkinson, Simon J., Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Bacallao, Robert L., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Sulfotransferases are enzymes responsible for xenobiotic detoxification. Mechanistically, these enzymes add a sulfate group to xenobiotics which increases their water solubility and urinary excretion. We identified SULT1C2 in a proteomic screen of mitochondria isolated from ischemic preconditioned kidneys. Using hydrodynamic gene delivery, we show that SULT1C2 protects against subsequent ischemia one week after gene delivery.

Methods

To determine SULT1C2’s mechanism of action, we assayed mitochondria function with and without human recombinant SULT1C2 and its substrate, 3’ Phosophoadenosine-5’-phosophosulfate (PAPS). Mitochondria respiration was assayed using an Oroboros Oxygraph O2K.

Results

We found that that PAPS and SULT1C2 incubated with mitochondria increase mitochondria state 3 respiration (from 139.4 ±36 to 370.7 ±32 pmol/min/mg) , following succinate and rotenone addition, 2.7-fold compared to mitochondria (P<0.05). The increase in SULT1C2/PAPS dependent respiration was inhibitable with antimycin A but not rotenone.

Conclusion

In conclusion SULT1C2 and PAPS increase the efficiency of complex II respiration indicating a potential change in the movement if electrons through the complex culminating in increased oxidative phosphorylation. This is a novel new function for an enzyme that heretofore was considered to be solely involved in detoxifying xenobiotics.

Funding

  • NIDDK Support