Recently, Professor Ma Chunhong's research group from the School of Basic Medical Sciences, Shandong University published a research paper entitled "ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury" in in Nature Communications. The work revealed ZHX2 as a negative regulator of mitochondrial function in acute liver injuries. Professor Ma Chunhong and Professor Yue Xuetian are co-corresponding authors of this article. Postdoctor Zhang Yankun is the first author. Shandong University is the first author's and corresponding author's affiliation.

Liver is the largest internal organ of human body and is responsible for life functions with metabolism, immunity, digestion, detoxification, and protein synthesis, which is characterized by the robust self-protective capacity of regeneration in response to injury. Mitochondria dysfunction contributes to acute liver injuries, and mitochondrial regulator, affects repair of liver injuries. 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 not only transcriptionally inhibits the expression of several mitochondrial electron transport chain genes but also decreases PGC-1α stability, leading to a reduction of mitochondrial mass and Oxidative phosphorylation (OXPHOS). Loss of Zhx2 promotes liver recovery after injury by increasing mitochondrial OXPHOS in mice treated with 2/3 partial hepatectomy or CCl4, and inhibition of PGC-1α or electron transport chain abolishes these effects. Notably, ZHX2 expression is higher in liver tissues of patients with drug-induced liver injury and is negatively correlated with mitochondrial mass marker TOM20. Delivering of shRNA targeting Zhx2 effectively protects mice from CCl4-induced liver injury. These results data clarify ZHX2 as a negative regulator of mitochondrial OXPHOS and a potential target for developing strategies for improving liver recovery after acute injuries.

Professor Ma Chunhong's team has been committed to basic and intervention strategies for the development of liver-related diseases, and they have achieved a series of high-level research outcomes. This work was supported by the National Natural Science Foundation of China, Taishan Scholarship, Shandong Natural Science Foundation and Collaborative Innovation Centre of Technology and Equipment for Biological Diagnosis and Therapy in the Universities of Shandong.

Link to the paper：https://www.nature.com/articles/s41467-023-43439-0