ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.
ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.
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DOI：
10.1038/s41467-023-43439-0
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发表时间：
2023-11-18
影响因子：
16.6
通讯作者：
Ma, Chunhong
中科院分区：
文献类型：
--
作者：
Zhang, Yankun;Fan, Yuchen;Hu, Huili;Zhang, Xiaohui;Wang, Zehua;Wu, Zhuanchang;Wang, Liyuan;Yu, Xiangguo;Song, Xiaojia;Xiang, Peng;Zhang, Xiaodong;Wang, Tixiao;Tan, Siyu;Li, Chunyang;Gao, Lifen;Liang, Xiaohong;Li, Shuijie;Li, Nailin;Yue, Xuetian;Ma, Chunhong
线粒体功能障碍有助于急性肝损伤，线粒体调节因子，如PGC-1α和MCJ，影响肝脏再生。因此，鉴定线粒体调节剂可能为开发治疗策略铺平道路。在这里，ZHX2被确定为急性肝损伤期间的线粒体调节因子。ZHX2转录抑制几个线粒体电子传递链基因的表达，降低PGC-1α的稳定性，导致线粒体质量和OXPHOS的减少。在部分肝切除或ccl4诱导的肝损伤小鼠中，缺失Zhx2通过增加线粒体OXPHOS促进肝脏恢复，而抑制PGC-1α或电子传递链可消除这些作用。值得注意的是，ZHX2在药物性肝损伤患者的肝组织中表达较高，且与线粒体质量标志物TOM20呈负相关。递送靶向Zhx2的shRNA可有效保护ccl4诱导的小鼠肝损伤。总之，我们的数据阐明了ZHX2是线粒体OXPHOS的负调节因子，也是开发改善急性损伤后肝脏恢复策略的潜在靶点。线粒体功能障碍可导致急性肝损伤。Zhang等发现Zhx2缺失通过PGC-1α依赖和独立的方式促进电子传递链基因的表达，从而增强线粒体功能。
Mitochondria dysfunction contributes to acute liver injuries, and mitochondrial regulators, such as PGC-1α 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-1α 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-1α 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. Mitochondria dysfunction contributes to acute liver injuries. Zhang et al. find that Zhx2 deletion enhances mitochondrial function by promoting electron transport chain gene expression via PGC-1α dependent and independent manner.
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DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
影响因子：
7.1
作者：
Fernandez-Marcos, Pablo J.;Auwerx, Johan
通讯作者：
Auwerx, Johan
影响因子：
4.8
作者：
El-Mir, MY;Nogueira, V;Leverve, X
通讯作者：
Leverve, X
影响因子：
11.8
作者：
Caldez, Matias J.;Van Hul, Noemi;Kaldis, Philipp
通讯作者：
Kaldis, Philipp
影响因子：
9
作者：
Lei, Xiaohua;Liu, Qiang;Qin, Wei;Tong, Qing;Li, Zhenghao;Xu, Wendi;Liu, Guoxing;Fu, Jie;Zhang, Ju;Kuang, Tao;Shao, Yaoli;Liu, Chun;Fang, Yu;Cao, Zhenyu;Yan, Likun;Liu, Zhiqiang;Liu, Siyuan;Yamamoto, Hirofumi;Mori, Masaki;Liang, Xinmin;Xu, Xundi
通讯作者：
Xu, Xundi