IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43439-0.html
   My bibliography  Save this article

ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury

Author

Listed:
  • Yankun Zhang

    (Cheeloo Medical College of Shandong University)

  • Yuchen Fan

    (Qilu Hospital of Shandong University)

  • Huili Hu

    (Shandong University)

  • Xiaohui Zhang

    (Shandong University)

  • Zehua Wang

    (Cheeloo Medical College of Shandong University)

  • Zhuanchang Wu

    (Cheeloo Medical College of Shandong University)

  • Liyuan Wang

    (Cheeloo Medical College of Shandong University)

  • Xiangguo Yu

    (Cheeloo Medical College of Shandong University)

  • Xiaojia Song

    (Cheeloo Medical College of Shandong University)

  • Peng Xiang

    (Cheeloo Medical College of Shandong University)

  • Xiaodong Zhang

    (Cheeloo Medical College of Shandong University)

  • Tixiao Wang

    (Cheeloo Medical College of Shandong University)

  • Siyu Tan

    (Cheeloo Medical College of Shandong University)

  • Chunyang Li

    (Cheeloo Medical College of Shandong University
    Shandong University)

  • Lifen Gao

    (Cheeloo Medical College of Shandong University)

  • Xiaohong Liang

    (Cheeloo Medical College of Shandong University)

  • Shuijie Li

    (Harbin Medical University)

  • Nailin Li

    (Karolinska Institute)

  • Xuetian Yue

    (Cheeloo Medical College of Shandong University
    Shandong University)

  • Chunhong Ma

    (Cheeloo Medical College of Shandong University)

Abstract

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.

Suggested Citation

  • Yankun Zhang & Yuchen Fan & Huili Hu & Xiaohui Zhang & Zehua Wang & Zhuanchang Wu & Liyuan Wang & Xiangguo Yu & Xiaojia Song & Peng Xiang & Xiaodong Zhang & Tixiao Wang & Siyu Tan & Chunyang Li & Life, 2023. "ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43439-0
    DOI: 10.1038/s41467-023-43439-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43439-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43439-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jin Zhou & Jeremy Pang & Madhulika Tripathi & Jia Pei Ho & Anissa Anindya Widjaja & Shamini Guna Shekeran & Stuart Alexander Cook & Ayako Suzuki & Anna Mae Diehl & Enrico Petretto & Brijesh Kumar Sing, 2022. "Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiangli Jiang & Ali Hyder Baig & Giuliana Palazzo & Rossella Pizzo & Toman Bortecen & Sven Groessl & Esther A. Zaal & Cinthia Claudia Amaya Ramirez & Alexander Kowar & Daniela Aviles-Huerta & Celia R., 2024. "P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Guoshu Bi & Jiaqi Liang & Yunyi Bian & Guangyao Shan & Yiwei Huang & Tao Lu & Huan Zhang & Xing Jin & Zhencong Chen & Mengnan Zhao & Hong Fan & Qun Wang & Boyi Gan & Cheng Zhan, 2024. "Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43439-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.