Changes in energy metabolism due to acute rotenone-induced mitochondrial complex I dysfunction – An in vivo large animal model

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7 Citations (SciVal)

Abstract

Metabolic crisis is a clinical condition primarily affecting patients with inherent mitochondrial dysfunction in situations of augmented energy demand. To model this, ten pigs received an infusion of rotenone, a mitochondrial complex I inhibitor, or vehicle. Clinical parameters, blood gases, continuous indirect calorimetry, in vivo muscle oxygen tension, ex vivo mitochondrial respiration and metabolomics were assessed. Rotenone induced a progressive increase in blood lactate which was paralleled by an increase in oxygen tension in venous blood and skeletal muscle. There was an initial decrease in whole body oxygen utilization, and there was a trend towards inhibited mitochondrial respiration in platelets. While levels of succinate were decreased, other intermediates of glycolysis and the TCA cycle were increased. This model may be suited for evaluating pharmaceutical interventions aimed at counteracting metabolic changes due to complex I dysfunction.

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalMitochondrion
Volume31
DOIs
Publication statusPublished - 2016 Nov 1

Subject classification (UKÄ)

  • Cell and Molecular Biology

Keywords

  • Animal model
  • Complex I
  • Energy metabolism
  • Metabolic crisis
  • Mitochondria

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