SIRT3 protects kidneys from ischemia-reperfusion injury by modulating the DRP1 pathway to induce mitochondrial autophagy.
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| Abstract |
Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) and may influence renal graft survival. In this study, we investigate the involvement of SIRT3 and DRP1 in mitochondrial autophagy and AKI in a mouse model of IRI. Autophagy was detected in the absence of SIRT3, and hypoxic reoxygenation (H/R) experiments using renal tubular epithelial cells NRK52E were performed in vitro to validate these results. We found that autophagosomes increased following IRI and that the expression of autophagy-related genes was up-regulated. The inhibition of autophagy with 3-methyladenine exacerbated IRI, whereas the DRP1 inhibitor Mdivi-1 reversed this inhibition. Mdivi-1 did not reverse the inhibition of autophagy in the absence of SIRT3. During IRI, Mdivi-1 reduced autophagy and DRP1 expression, whereas SIRT3 overexpression attenuated this condition. Rescue experiment showed that autophagy was increased when both SIRT3 or DRP1 were over- or under-expressed or just DRP1 was under-expressed but expression was reduced when just SIRT3 was under-expressed. However, the expression of DRP1-related molecules was reduced when SIRT3 was overexpressed and when DRP1 was under-expressed. Taken together, these findings indicate that SIRT3 protects against kidney damage from IRI by modulating the DRP1 pathway to induce mitochondrial autophagy.
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| Authors | Wenyu Zhao, Mingxing Sui, Rui Chen, Hanlan Lu, Youhua Zhu, Lei Zhang, Li Zeng |
| Journal | Life sciences (Life Sci) Vol. 286 Pg. 120005 (Dec 01 2021) ISSN: 1879-0631 [Electronic] Netherlands |
| PMID | 34606850 (Publication Type: Journal Article) |
| Copyright | Copyright © 2021. Published by Elsevier Inc. |
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