The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation

• DOI: 10.1016/j.apsb.2023.01.019
• Publication Date: 2023-01-29T14:57:55Z
• Authors: Yiwei Zhu; Lin Lei; Xinghui Wang; Linfang Chen; Wei Li; Jinxia Li; Chenchen Zhao; Xiliang Du; Yuxiang Song; Wenwen Gao; Guowen Liu; Xinwei Li
• Keywords: NEDD4; VDAC1

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) an E3 ubiquitin ligase that has been implicated in the pathogenesis numerous diseases; however, its role APAP-induced injury (AILI) unclear. Thus, this study aimed to investigate NEDD4-1 AILI. We found was dramatically response APAP treatment mouse livers and isolated hepatocytes. Hepatocyte-specific knockout exacerbated mitochondrial damage resultant hepatocyte necrosis injury, while hepatocyte-specific overexpression mitigated these pathological events both vivo vitro. Additionally, deficiency led marked accumulation voltage-dependent anion channel 1 (VDAC1) increased VDAC1 oligomerization. Furthermore, knockdown alleviated AILI weakened exacerbation caused by deficiency. Mechanistically, interact with PPTY motif through WW domain regulate K48-linked ubiquitination degradation VDAC1. Our present indicates suppressor functions regulating