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Author Spotlight: Advanced Integrated Model for Sepsis-Induced Myopathy and Single-Cell Metabolic Analysis
Published on: June 14, 2024
Causal Relationship between Mitochondrial-Associated Proteins and Sepsis in ICU Patients: A Mendelian Randomization
Jian Zhao1, Shu-Qin Zhou1, Yu-Xing Chen2
1Department of Emergency, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072,China.
Background:
The alarming mortality rate of sepsis in ICUs has garnered significant attention. The precise etiology remains elusive. Mitochondria, often referred to as the cellular powerhouses, have been postulated to have a dysfunctional role, correlating with the onset and progression of sepsis. However, the exact causal relationship remains to be defined.
Method:
Employing the Mendelian randomization approach, this study systematically analyzed data from the IEUOpenGWAS and UKbiobank databases concerning mitochondrial function-related proteins and their association with sepsis, aiming to delineate the causal relationship between the two.
Results:
The findings underscored a statistically significant association of GrpE1 with sepsis, registering a P value of 0.005 and an OR of 0.499 (95% CI: 0.307-0.810). Likewise, HTRA2, ISCU, and CUP3 each manifested significant associations with sepsis, yielding OR values of 0.585, 0.637, and 0.634, respectively. These results suggest potential implications of the aforementioned proteins in the pathogenesis of sepsis.
Conclusion:
The present study furnishes novel evidence elucidating the roles of GrpE1, HTRA2, ISCU, and CUP3 in the pathophysiology of sepsis. Such insights pave the way for a deeper understanding of the pathological mechanisms underpinning sepsis and hint at promising therapeutic strategies for the future.
Insights
This study found that specific mitochondrial proteins, including GrpE1, HTRA2, ISCU, and CUP3, are causally linked to sepsis. These findings offer new insights into sepsis pathogenesis and potential therapeutic targets.
Area of Science:
- Biochemistry
- Genetics
- Critical Care Medicine
Background:
- Sepsis presents a high mortality rate in intensive care units (ICUs), with its exact causes still under investigation.
- Mitochondrial dysfunction is suspected to play a role in sepsis development and progression, but a definitive causal link is lacking.
Purpose of the Study:
- To investigate the causal relationship between mitochondrial function-related proteins and sepsis.
- To identify specific proteins involved in the pathophysiology of sepsis.
Main Methods:
- Utilized a Mendelian randomization approach.
- Analyzed data from the IEUOpenGWAS and UKbiobank databases.
Main Results:
- Identified a statistically significant association between GrpE1 and sepsis (P=0.005, OR=0.499).
- Found significant associations for HTRA2 (OR=0.585), ISCU (OR=0.637), and CUP3 (OR=0.634) with sepsis.
- These proteins may play a role in the pathogenesis of sepsis.
Conclusions:
- Provided novel evidence for the involvement of GrpE1, HTRA2, ISCU, and CUP3 in sepsis pathophysiology.
- These findings enhance understanding of sepsis mechanisms.
- Suggests potential avenues for future therapeutic strategies in sepsis treatment.
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