Dynamin-related protein 1 deficiency promotes recovery from AKI

Heather M. Perry, Liping Huang, Rebecca J. Wilson, Amandeep Bajwa, Hiromi Sesaki, Zhen Yan, Diane L. Rosin, David F. Kashatus, Mark D. Okusa

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 b-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.

Original languageEnglish (US)
Pages (from-to)194-206
Number of pages13
JournalJournal of the American Society of Nephrology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2018

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Dynamins
Protein Deficiency
Kidney
Mitochondrial Dynamics
Proteins
Fibrosis
Hydroxybutyrates
Genetic Models
Wounds and Injuries
Reperfusion Injury
Oxidative Stress
Cell Death
Ischemia
Epithelium
Inflammation

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Perry, H. M., Huang, L., Wilson, R. J., Bajwa, A., Sesaki, H., Yan, Z., ... Okusa, M. D. (2018). Dynamin-related protein 1 deficiency promotes recovery from AKI. Journal of the American Society of Nephrology, 29(1), 194-206. https://doi.org/10.1681/ASN.2017060659

Dynamin-related protein 1 deficiency promotes recovery from AKI. / Perry, Heather M.; Huang, Liping; Wilson, Rebecca J.; Bajwa, Amandeep; Sesaki, Hiromi; Yan, Zhen; Rosin, Diane L.; Kashatus, David F.; Okusa, Mark D.

In: Journal of the American Society of Nephrology, Vol. 29, No. 1, 01.01.2018, p. 194-206.

Research output: Contribution to journalArticle

Perry, HM, Huang, L, Wilson, RJ, Bajwa, A, Sesaki, H, Yan, Z, Rosin, DL, Kashatus, DF & Okusa, MD 2018, 'Dynamin-related protein 1 deficiency promotes recovery from AKI', Journal of the American Society of Nephrology, vol. 29, no. 1, pp. 194-206. https://doi.org/10.1681/ASN.2017060659
Perry, Heather M. ; Huang, Liping ; Wilson, Rebecca J. ; Bajwa, Amandeep ; Sesaki, Hiromi ; Yan, Zhen ; Rosin, Diane L. ; Kashatus, David F. ; Okusa, Mark D. / Dynamin-related protein 1 deficiency promotes recovery from AKI. In: Journal of the American Society of Nephrology. 2018 ; Vol. 29, No. 1. pp. 194-206.
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