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.
(Less)
- author
- 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
- organization
- publishing date
- 2016-11-01
- 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
-
- pmid:27769952
- wos:000388431500007
- scopus:84995487542
- ISSN
- 1567-7249
- DOI
- 10.1016/j.mito.2016.10.003
- project
- Development of treatment for mitochondrial disorders
- Mitochondrial dysfunction in drug and chemical toxicity: mechanism, target identification and therapeutic development
- language
- English
- LU publication?
- yes
- id
- b2f228ab-5921-4a1e-872f-57f212b58106
- date added to LUP
- 2016-12-05 11:09:55
- date last changed
- 2024-11-02 10:06:35
@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}},
keywords = {{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}},
doi = {{10.1016/j.mito.2016.10.003}},
volume = {{31}},
year = {{2016}},
}