Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI
Year: 2017
Type: article
Abstract: The proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective β -hydroxybutyrate signaling pathway. Loss of DRP1 preserved mitochondrial structure and reduced oxidative stress in injured kidneys. Lastly, proximal tubule deletion of DRP1 after ischemia-reperfusion injury attenuated progressive kidney injury and fibrosis. These results implicate DRP1 and mitochondrial dynamics as an important mediator of AKI and progression to fibrosis and suggest that DRP1 may serve as a therapeutic target for AKI.
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1435875440, G1548338793, AMPK-Ulk1 in Exercise-Induced Mitophagy in Skeletal Muscle, Endothelial sphingosine-1-phosphate receptor 1 regulates renal recovery after acute kidney injury, G3732544654, Kidney Disease and Inflammation, MBF Bioscience and Zeiss Microscope System for Stereology and Tissue Morphology, Exploring the Role of Mitochondrial Fission in Pancreatic Tumorigenesis, Sphingolipids in Acute Kidney Injury and Disease Progression, G897168839, G961811102
OpenAlex ID: W2766902151