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Updated: Apr 28, 2026
Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
Sirtuin 4 Knockout Aggravates Sepsis-Induced Acute Liver Injury by Enhancing Mitochondrial Fission and Mitophagy in
1Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China, cqmu.edu.cn.
Background:
Sepsis leads to multiorgan damage, with the liver being the main target. Sirtuin 4 (Sirt4) plays a regulatory role in mitochondrial function and metabolism, but its mechanism in liver injury caused by sepsis remains unclear.
Methods:
The mouse model of liver injury caused by sepsis was established by cecal ligation and puncture (CLP) surgery. The degree of liver injury in wild-type (WT) and Sirt4 gene total knockout (Sirt4-KO) mice was compared by serum AST, alanine aminotransferase (ALT), and histological analysis. The expression of mitophagy and mitochondrial dynamic indicators was detected by biochemical experiments.
Results:
Liver injury in Sirt4-KO mice was more severe than that in WT mice after CLP, manifested as significant upregulation of mitophagy and mitochondrial dynamics imbalance. Mechanistically, Sirt4 deficiency increases mitochondrial fission and mitophagy, thereby leading to cellular damage.
Conclusions:
Sirt4 knockout (KO) aggravates liver injury in sepsis through increasing mitochondrial fission and mitophagy, which indicates a promising direction for future clinical treatment.
Insights
Sepsis exacerbates liver injury in Sirtuin 4 knockout mice by increasing mitochondrial fission and mitophagy. This finding highlights Sirt4
Area of Science:
- Mitochondrial biology
- Organ injury
- Sepsis research
Background:
- Sepsis commonly causes multiorgan damage, particularly affecting the liver.
- Sirtuin 4 (Sirt4) influences mitochondrial function and metabolism, but its role in sepsis-induced liver injury is not well understood.
Purpose of the Study:
- To investigate the role of Sirtuin 4 (Sirt4) in sepsis-induced liver injury.
- To elucidate the underlying mechanisms involving mitochondrial dynamics and mitophagy.
Main Methods:
- Established a mouse model of sepsis-induced liver injury using cecal ligation and puncture (CLP).
- Compared liver injury severity in wild-type (WT) and Sirt4 knockout (Sirt4-KO) mice.
- Analyzed serum liver enzymes (AST, ALT), histological damage, and mitochondrial indicators (mitophagy, dynamics).
Main Results:
- Sepsis induced more severe liver injury in Sirt4-KO mice compared to WT mice.
- Sirt4 deficiency led to increased mitophagy and imbalanced mitochondrial dynamics (fission).
- These changes mechanistically contribute to cellular damage in sepsis-induced liver injury.
Conclusions:
- Sirtuin 4 knockout exacerbates sepsis-induced liver injury by promoting mitochondrial fission and mitophagy.
- Targeting Sirt4-mediated pathways presents a potential therapeutic strategy for sepsis-related liver damage.
