| First Author | Xu M | Year | 2021 |
| Journal | Cell Mol Gastroenterol Hepatol | Volume | 12 |
| Issue | 2 | Pages | 567-584 |
| PubMed ID | 33766785 | Mgi Jnum | J:329969 |
| Mgi Id | MGI:6815604 | Doi | 10.1016/j.jcmgh.2021.03.007 |
| Citation | Xu M, et al. (2021) DJ-1 Deficiency in Hepatocytes Improves Liver Ischemia-Reperfusion Injury by Enhancing Mitophagy. Cell Mol Gastroenterol Hepatol 12(2):567-584 |
| abstractText | BACKGROUND & AIMS: DJ-1 is universally expressed in various tissues and organs and is involved in the physiological processes in various liver diseases. However, the role of DJ-1 in liver ischemia-reperfusion (I/R) injury is largely unknown. METHODS: In this study, we first examined the DJ-1 expression changes in the liver tissues of mice and clinical donor after hepatic I/R by both quantitative polymerase chain reaction and Western blotting assays. Then we investigated the role of DJ-1 in I/R injury by using a murine liver I/R model. RESULTS: We demonstrated that DJ-1 down-regulation in both human and mouse liver tissues in response to I/R injury and Dj-1 deficiency in hepatocytes but not in myeloid cells could significantly ameliorate I/R induced liver injury and inflammatory responses. This hepatoprotective effect was dependent on enhanced autophagy in Dj-1 knockout mice, because inhibition of autophagy by 3-methyladenine and chloroquine could reverse the protective effect on hepatic I/R injury in Dj-1 knockout mice. CONCLUSIONS: Dj-1 deficiency in hepatocytes significantly enhanced mitochondrial accumulation and protein stability of PARKIN, which in turn promotes the onset of mitophagy resulting in elevated clearance of damaged mitochondria during I/R injury. |
