Abstract: FR-PO171

The Role of a Novel Mitochondrial Protease, OMA1, During Renal Cold Storage and Rewarming

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

  • Tobacyk, Julia, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • MacMillan-Crow, Lee Ann, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Parajuli, Nirmala, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Shrum, Stephen A, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
Background

Most kidney transplants come from deceased donors. These kidneys must undergo cold preservation before transplantation to maintain function of the organ during storage so that the graft will function at reperfusion. However, cold storage (CS) can result in renal and mitochondrial damage impairing overall graft outcome. OMA1 is a novel metallopeptidase in the mitochondria that plays a key role in mitochondrial dynamics. The goal of this study is to determine the role of OMA1 during renal CS in an in vitro model. Specifically, we will investigate the interaction of key proteins that regulate the fission and fusion machinery in the mitochondria such as OMA1, YME1L and OPA1.

Methods

Both rat and human normal proximal tubular kidney cells were exposed to 18 hr of CS followed by rewarming (CS/RW) for 6 hr. Expression of OMA1, YME1L, and OPA1 were assessed using western blot analysis. The interaction between these proteins was determined via OMA1 siRNA silencing techniques and OMA1 co-immunoprecipitation.

Results

In our studies we show that OMA1 expression is altered during CS both in rat and human normal proximal tubular kidney cells. Furthermore, expression of the long form of OPA1 is decreased in CS/RW suggesting compromised mitochondrial fusion. Our initial studies with OMA1 siRNA studies show successful knockdown, and further experiments will assess how OMA1 knockdown affects YME1L and OPA1.

Conclusion

Overall, CS initiates impairment of proteins related to mitochondrial fission and fusion. Our preliminary data suggest that OMA1 may be a promising therapeutic target for improving the function of kidneys transplanted after CS.

Funding

  • Other NIH Support