A mouse model of mitochondrial complex III dysfunction induced by myxothiazol.
Biochem Biophys Res Commun
; 446(4): 1079-84, 2014 Apr 18.
Article
in En
| MEDLINE
| ID: mdl-24661880
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 0.56 mg/kg to C57Bl/J6 mice every 24 h 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 2 h post-injection. At 74 h 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Electron Transport Complex III
/
Liver
/
Mitochondria
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Antifungal Agents
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2014
Document type:
Article
Affiliation country:
Suecia