2. Academic Validation
  3. ATP6V0d2 alleviates acute liver injury via promoting hepatocyte autophagy

ATP6V0d2 alleviates acute liver injury via promoting hepatocyte autophagy

  • Biochim Biophys Acta Mol Basis Dis. 2026 Apr;1872(4):168170. doi: 10.1016/j.bbadis.2026.168170.
Mengxia Zhang 1,  Zhemin Shi 2,  Yi Yang 2,  Yue Huang 3,  Kefei Guo 2,  Yuying Sun 2,  Jianan Gao 4,  Jiajun Wang 2,  Yanjun Li 5,  Wei Hong 6,  Tao Han 7,  Kun Zhang 8
Affiliations

Affiliations

  • 1 Department of Histology and Developmental Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Clinical Laboratory, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, China.
  • 2 Department of Histology and Developmental Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 3 Department of Hepatology and Gastroenterology, Tianjin Union Medical Center, Tianjin Medical University, The First Affiliated Hospital of Nankai University, Tianjin, China.
  • 4 The Second Clinical Medical College of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
  • 5 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
  • 6 Department of Histology and Developmental Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Electronic address: [email protected].
  • 7 Department of Hepatology and Gastroenterology, Tianjin Union Medical Center, Tianjin Medical University, The First Affiliated Hospital of Nankai University, Tianjin, China. Electronic address: [email protected].
  • 8 Department of Histology and Developmental Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Electronic address: [email protected].
PMID: 41604740 DOI: 10.1016/j.bbadis.2026.168170
Abstract

Liver injury is the pathological basis of various liver diseases, and severe acute liver injury can progress to acute liver failure with a high mortality. Although continuous progress has been made over the past few decades, the molecular mechanism underlying the progress of acute liver injury is still unclear. ATP6V0d2, a subunit of the vacuolar ATPase (V-ATPase) complex, is implicated in organelle acidification and intracellular degradation processes. In this study, three liver injury datasets were analyzed to screen the differentially expressed genes (DEGs) and identify Atp6v0d2, which was initially downregulated, and then upregulated to slightly higher than normal levels in both hepatocytes (HCs) and liver tissues in carbon tetrachloride (CCl4)-induced acute liver injury, with the most significant downregulation observed 24 h after CCl4 injection. Moreover, hepatocyte-specific overexpression of ATP6V0d2 alleviated CCl4, concanavalin A (ConA) and acetaminophen (APAP)-induced acute liver injury by promoting hepatocyte Autophagy, while silencing ATP6V0d2 inhibited hepatocyte Autophagy and aggravated liver injury in vivo. In addition, consistent with the results of gene enrichment analysis, in vitro data demonstrated that ATP6V0d2 promoted hepatocyte Autophagy mainly via facilitating the formation of autophagosomes. In conclusion, our results demonstrated that ATP6V0d2 played a protective role in acute liver injury by facilitating hepatocyte Autophagy, which may provide a theoretical basis for the treatment and prognosis of acute liver injury.

Keywords

ATP6V0d2; Acute liver injury; Autophagy; Hepatocyte.

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