2. Academic Validation
  3. Sentrin-specific protease 1 maintains mitochondrial homeostasis through targeting the deSUMOylation of sirtuin-3 to alleviate oxidative damage induced by hepatic ischemia/reperfusion

Sentrin-specific protease 1 maintains mitochondrial homeostasis through targeting the deSUMOylation of sirtuin-3 to alleviate oxidative damage induced by hepatic ischemia/reperfusion

  • Free Radic Biol Med. 2023 Dec 3:S0891-5849(23)01141-3. doi: 10.1016/j.freeradbiomed.2023.11.040.
Kang Xia 1,  Jiayu Guo 2,  Bo Yu 1,  Tianyu Wang 1,  Qiangmin Qiu 2,  Qi Chen 2,  Tao Qiu 3,  Jiangqiao Zhou 4,  Shusen Zheng 5
Affiliations

Affiliations

  • 1 Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, China; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China; Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, China; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 3 Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, China; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: qiutao@whu.edu.cn.
  • 4 Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, China; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: zhoujq@whu.edu.cn.
  • 5 Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China. Electronic address: shusenzheng@zju.edu.cn.
PMID: 38052275 DOI: 10.1016/j.freeradbiomed.2023.11.040
Abstract

Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes a substantial economic burden in clinical practice, especially in liver surgery. Sentrin-specific protease 1 (SENP1) is a crucial Enzyme involved in the regulation of SUMOylation, and is related to various diseases. However, the role of SENP1 in HIRI remains unexplored. Here, we confirmed that SENP1 actively participated in modulating the oxidative damage induced by HIRI. Notably, SENP1 functioned by maintaining mitochondrial homeostasis. Further mechanistic exploration indicated that the protective mitochondrial protein sirtuin-3 (SIRT3) was inactivated by SUMOylation during HIRI, which was reversed by SENP1. Overexpression of SENP1 could restore mitochondrial function, mitigate oxidative stress and attenuated Apoptosis through recovering the expression of SIRT3 during HIRI. Nevertheless, 3-TYP, an inhibitor of SIRT3, could eliminate the therapeutic effects brought by overexpression of SENP1. In conclusion, our findings demonstrated that SENP1 mediated the deSUMOylation of SIRT3 and maintained mitochondrial homeostasis, thus alleviating HIRI induced oxidative damage. SENP1 might be a promising therapeutic target for HIRI.

Keywords

Hepatic ischemia-reperfusion injury; Mitochondrial homeostasis; Oxidative damage; SENP1; SUMOylation; Sirt3.

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