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

Karlsson, Michael LU ; Ehinger, Johannes K. LU ; Piel, Sarah LU ; Sjövall, Fredrik LU ; Henriksnäs, Johanna; Höglund, Urban; Hansson, Magnus J. LU and Elmér, Eskil LU (2016) In Mitochondrion 31. p.56-62
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animal model, Complex I, Energy metabolism, Metabolic crisis, Mitochondria
in
Mitochondrion
volume
31
pages
7 pages
publisher
Elsevier
external identifiers
  • scopus:84995487542
  • wos:000388431500007
ISSN
1567-7249
DOI
10.1016/j.mito.2016.10.003
language
English
LU publication?
yes
id
b2f228ab-5921-4a1e-872f-57f212b58106
date added to LUP
2016-12-05 11:09:55
date last changed
2017-09-18 11:30:07
@article{b2f228ab-5921-4a1e-872f-57f212b58106,
  abstract     = {<p>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.</p>},
  author       = {Karlsson, Michael and Ehinger, Johannes K. and Piel, Sarah and Sjövall, Fredrik and Henriksnäs, Johanna and Höglund, Urban and Hansson, Magnus J. and Elmér, Eskil},
  issn         = {1567-7249},
  keyword      = {Animal model,Complex I,Energy metabolism,Metabolic crisis,Mitochondria},
  language     = {eng},
  month        = {11},
  pages        = {56--62},
  publisher    = {Elsevier},
  series       = {Mitochondrion},
  title        = {Changes in energy metabolism due to acute rotenone-induced mitochondrial complex I dysfunction – An in vivo large animal model},
  url          = {http://dx.doi.org/10.1016/j.mito.2016.10.003},
  volume       = {31},
  year         = {2016},
}