New Study from Sims-Lucas Laboratory Finds Protective Metabolic Response in Acute Kidney Injury from Succinylation of Park7
June 20, 2024
The Sims-Lucas Laboratory in the Division of Pediatric Nephrology at UPMC Children’s Hospital of Pittsburgh published new findings on the protective metabolic responses in acute kidney injury (AKI).
The multidisciplinary team, including colleagues from the Goetzman Laboratory in the Division of Genetic and Genomic Medicine at UPMC Children’s and collaborators at the Buck Institute for Research on Aging in California found an important role for lysine succinylation with the Park7 protein in modulating cellular responses to ischemic damage in the kidneys.
The study was published in the American Journal of Physiology-Renal Physiology in May 2024. Katherine Pfister, PhD, was the study’s first author, and Sunder Sims-Lucas, PhD, principal investigator in the Sims-Lucas lab was the senior author.
“Our research demonstrates that the succinylation of Park7 not only enhances peroxisomal activity but also activates a metabolic response that mitigates oxidative stress,” says Dr. Sims-Lucas. “This may open up possible new angles for therapeutic intervention for treating or preventing AKI in certain circumstances.”
Study Overview and Findings Highlights
Previous research by Dr. Sims-Lucas and colleagues has found that protein hypersuccinylation, following the depletion of the desuccinylase Sirtuin 5, was found to provide some protection against kidney injury in the proximal tubules. Building on these findings, the current study explored the role of Park7, a protein associated with neuroprotection, antioxidative activity, gene regulation, and other processes, in mediating these protective effects after undergoing lysine succinylation, which is a posttranslational modification that can significantly alter the properties or functionality of proteins.
Among the study’s findings, the team demonstrated that succinylation of Park7 activates a metabolic response that enhances peroxisomal activity and protects against ischemic AKI.
The team’s experiments showed that Park7 plays a role in mitigating oxidative damage and promoting cellular resilience. The research also revealed that hypersuccinylation of proteins, including Park7, leads to an upregulation of peroxisomal functions, which are important for cellular detoxification and maintaining metabolic balance.
Furthermore, the protective role of Park7 observed in the study aligns with previous research indicating its beneficial effects in cardiovascular damage and chronic kidney disease. These findings suggest that succinylation of Park7 not only helps in reducing acute kidney damage but may also prevent the progression of AKI to chronic kidney disease by working to reduce cellular oxidative stress.
Clinical and Translational Implications of the Research
The findings from Dr. Sims-Lucas and colleague’s study point at a novel mechanism that could be targeted for therapeutic intervention in AKI.
The potential therapeutic benefits of targeting Park7 succinylation may be significant in mitigating the effects of ischemic AKI and reduce the long-term risk of progression to chronic kidney disease.
For further details about the study, please use the link below.
Study Reference
Pfister K, Young V, Frankel B, et al. Succinylation of Park 7 Activates a Protective Metabolic Response to Acute Kidney Injury. Am J Physiol Renal Physiol. 2024. Online ahead of print.
Additional Reading
Learn more about the Sims-Lucas Lab and its research on the cellular mechanisms of AKI.
Learn more about the Goetzman Lab. and its research on fatty acid oxidation and its role in multiple disease processes, including AKI.
