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A mouse model of mitochondrial complex III dysfunction induced by myxothiazol.

Davoudi, Mina LU ; Kallijärvi, Jukka LU ; Marjavaara, Sanna; Kotarsky, Heike LU ; Hanson, Eva; Levéen, Per LU and Fellman, Vineta LU (2014) In Biochemical and Biophysical Research Communications 446(4). p.1079-1084
Abstract
Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIII inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56mg/kg to C57Bl/J6 mice every 24h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2h post-injection. At 74h only... (More)
Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIII inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56mg/kg to C57Bl/J6 mice every 24h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2h post-injection. At 74h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
446
issue
4
pages
1079 - 1084
publisher
Elsevier
external identifiers
  • pmid:24661880
  • wos:000335367900043
  • scopus:84899474468
ISSN
1090-2104
DOI
10.1016/j.bbrc.2014.03.058
language
English
LU publication?
yes
id
c3350de4-b642-4d1a-b10e-c38293eecb44 (old id 4379814)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24661880?dopt=Abstract
date added to LUP
2014-04-03 21:22:43
date last changed
2017-05-21 03:23:25
@article{c3350de4-b642-4d1a-b10e-c38293eecb44,
  abstract     = {Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIII inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56mg/kg to C57Bl/J6 mice every 24h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2h post-injection. At 74h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies.},
  author       = {Davoudi, Mina and Kallijärvi, Jukka and Marjavaara, Sanna and Kotarsky, Heike and Hanson, Eva and Levéen, Per and Fellman, Vineta},
  issn         = {1090-2104},
  language     = {eng},
  number       = {4},
  pages        = {1079--1084},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {A mouse model of mitochondrial complex III dysfunction induced by myxothiazol.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2014.03.058},
  volume       = {446},
  year         = {2014},
}