A mouse model of mitochondrial complex III dysfunction induced by myxothiazol

作者：Davoudi Mina; Kallijarvi Jukka; Marjavaara Sanna; Kotarsky Heike; Hansson Eva; Leveen Per; Fellman Vineta^*

来源：Biochemical and Biophysical Research Communications, 2014, 446(4): 1079-1084.

DOI：10.1016/j.bbrc.2014.03.058

• Respiratory chain complex III
• Chemical inhibition of complex III
• Mitochondria
• Experimental hepatopathy
• BCS1L
• Mouse model

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/16 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.

• 出版日期2014-4-18