Hepatic ischemia/reperfusion (I/R) injury is an important cause of liver function impairment following liver surgery. The ubiquitin-proteasome system (UPS) plays a crucial role in protein quality control and has substantial impact on the hepatic I/R process. Although OTU deubiquitinase 1 (OTUD1) is involved in diverse biological processes, its specific functional implications in hepatic I/R are not yet fully understood. This study demonstrates that OTUD1 alleviates oxidative stress, apoptosis, and inflammation induced by hepatic I/R injury. Mechanistically, OTUD1 deubiquitinates and activates nuclear factor erythroid 2-related factor 2 (NRF2) through its catalytic site cysteine 320 residue and ETGE motif, thereby attenuating hepatic I/R injury. Additionally, administration of a short peptide containing the ETGE motif significantly mitigates hepatic I/R injury in mice. Overall, our study elucidates the mechanism and role of OTUD1 in ameliorating hepatic I/R injury, providing a theoretical basis for potential treatment using ETGE-peptide.

中文翻译：

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去泛素酶 OTUD1 稳定 NRF2 以减轻肝缺血/再灌注损伤


肝脏缺血/再灌注（I/R）损伤是肝脏手术后肝功能损害的重要原因。泛素蛋白酶体系统 (UPS) 在蛋白质质量控​​制中发挥着至关重要的作用，并对肝脏 I/R 过程产生重大影响。尽管 OTU 去泛素酶 1 (OTUD1) 参与多种生物过程，但其在肝 I/R 中的具体功能意义尚未完全了解。这项研究表明 OTUD1 可以减轻肝 I/R 损伤引起的氧化应激、细胞凋亡和炎症。从机制上讲，OTUD1 通过其催化位点半胱氨酸 320 残基和 ETGE 基序去泛素化并激活核因子红细胞 2 相关因子 2 (NRF2)，从而减轻肝 I/R 损伤。此外，给予含有 ETGE 基序的短肽可显着减轻小鼠的肝缺血再灌注损伤。总体而言，我们的研究阐明了 OTUD1 在改善肝 I/R 损伤中的机制和作用，为使用 ETGE 肽进行潜在治疗提供了理论基础。