| First Author | Zhang Y | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 7527 |
| PubMed ID | 37980429 | Mgi Jnum | J:342959 |
| Mgi Id | MGI:7560850 | Doi | 10.1038/s41467-023-43439-0 |
| Citation | Zhang Y, et al. (2023) ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury. Nat Commun 14(1):7527 |
| abstractText | Mitochondria dysfunction contributes to acute liver injuries, and mitochondrial regulators, such as PGC-1alpha and MCJ, affect liver regeneration. Therefore, identification of mitochondrial modulators may pave the way for developing therapeutic strategies. Here, ZHX2 is identified as a mitochondrial regulator during acute liver injury. ZHX2 both transcriptionally inhibits expression of several mitochondrial electron transport chain genes and decreases PGC-1alpha stability, leading to reduction of mitochondrial mass and OXPHOS. Loss of Zhx2 promotes liver recovery by increasing mitochondrial OXPHOS in mice with partial hepatectomy or CCl4-induced liver injury, and inhibition of PGC-1alpha or electron transport chain abolishes these effects. Notably, ZHX2 expression is higher in liver tissues from patients with drug-induced liver injury and is negatively correlated with mitochondrial mass marker TOM20. Delivery of shRNA targeting Zhx2 effectively protects mice from CCl4-induced liver injury. Together, our data clarify ZHX2 as a negative regulator of mitochondrial OXPHOS and a potential target for developing strategies for improving liver recovery after acute injuries. |
