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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


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.


Enheter & grupper
Externa organisationer
  • Adlego Biomedical AB
  • NeuroVive Pharmaceutical AB

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi


Sidor (från-till)56-62
Antal sidor7
StatusPublished - 2016 nov 1
Peer review utfördJa

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