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Mitochondrial oxidative alterations following partial hepatectomy

F Guerrieri1, G Vendemiale, I Grattagliano

  • 1Institute of Medical Biochemistry and Chemistry and Centre for the Study of Mitochondria and Energy Metabolism (C.N.R.), University of Bari, Italy.

Free Radical Biology & Medicine
|January 16, 1999
PubMed
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Partial hepatectomy induces mitochondrial oxidative stress in regenerating rat livers. This stress damages ATP synthesis and alters key proteins like F0F1-ATP synthase, impacting oxidative phosphorylation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Hepatology

Background:

  • Liver regeneration is a complex process following partial hepatectomy.
  • Mitochondrial function is crucial for cellular energy production and homeostasis.
  • Oxidative stress is implicated in various cellular dysfunctions.

Purpose of the Study:

  • To investigate the impact of partial hepatectomy on mitochondrial function during early liver regeneration.
  • To determine if oxidative stress occurs in mitochondria post-hepatectomy.
  • To examine alterations in mitochondrial proteins, specifically F0F1-ATP synthase.

Main Methods:

  • Isolation of rat liver mitochondria at different time points after partial hepatectomy.
  • Measurement of ATP synthesis rates, malondialdehyde, oxidized proteins, and glutathione levels.

Related Experiment Videos

  • Analysis of mitochondrial protein thiol content and disulfide bond formation.
  • Blue-native gel electrophoresis to assess F0F1-ATP synthase complex integrity.
  • Electroelution and analysis of glutathione bound to F0F1-ATP synthase.

    • Main Results:

    • Mitochondria from regenerating livers showed decreased ATP synthesis rates.
    • Increased production of malondialdehyde and oxidized proteins indicated oxidative stress.
    • Reduced intramitochondrial glutathione and protein thiols, with increased glutathione disulfide bonds.
    • Progressive decrease in F0F1-ATP synthase content observed via blue-native gel electrophoresis.
    • Elevated glutathione binding to F0F1-ATP synthase during regeneration.

    Conclusions:

    • Partial hepatectomy induces significant mitochondrial oxidative stress in the early phase of liver regeneration.
    • Oxidative stress alters mitochondrial proteins involved in oxidative phosphorylation, exemplified by F0F1-ATP synthase.
    • These modifications can impair the efficiency of ATP synthesis and overall mitochondrial function.