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The Warburg Effect Promotes Mitochondrial Injury Regulated by Uncoupling Protein-2 in Septic Acute Kidney Injury
Ran Ji1, Weiwei Chen1, Yuming Wang1
1Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shock (Augusta, Ga.)
|June 5, 2020
Summary
Metabolism reprogramming, specifically the uncoupling protein-2 (UCP2)-regulated Warburg effect, promotes kidney mitochondrial injury during sepsis. Targeting aerobic glycolysis may offer a new treatment strategy for septic acute kidney injury.
Area of Science:
- Biochemistry
- Cell Biology
- Pathophysiology
Background:
- Metabolic reprogramming is increasingly linked to sepsis regulation.
- The role of metabolic changes in septic organ dysfunction, particularly kidney injury, is not fully understood.
- This study investigates the role of aerobic glycolysis in sepsis-induced kidney mitochondrial damage.
Purpose of the Study:
- To elucidate the mechanism of uncoupling protein-2 (UCP2)-regulated aerobic glycolysis in kidney injury during sepsis.
- To explore the potential of targeting aerobic glycolysis for treating septic acute kidney injury.
Main Methods:
- Sepsis was modeled in mice (cecal ligation puncture) and human kidney cells (HK-2 treated with lipopolysaccharide).
- Uncoupling protein-2 (UCP2) expression was knocked down using small interfering RNA.
- Glycolysis and oxidative phosphorylation were assessed using mass spectrometry, commercial kits, and oxygen consumption/extracellular acidification rate measurements.
Main Results:
- Septic tubular epithelial cells showed enhanced aerobic glycolysis.
- Inhibition of glycolysis partially restored mitochondrial function and reduced oxidative stress.
- Knockdown of UCP2 led to increased aerobic glycolysis and exacerbated mitochondrial injury.
Conclusions:
- Aerobic glycolysis, regulated by UCP2, plays a significant role in promoting kidney mitochondrial injury in sepsis.
- Targeting aerobic glycolysis presents a promising therapeutic approach for septic acute kidney injury.
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