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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Mina Davoudi
  • Jukka Kallijärvi
  • Sanna Marjavaara
  • Heike Kotarsky
  • Eva Hanson
  • Per Levéen
  • Vineta Fellman
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences
Original languageEnglish
Pages (from-to)1079-1084
JournalBiochemical and Biophysical Research Communications
Volume446
Issue number4
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Related research output

Davoudi, M., 2014, Paediatrics, Faculty of Medicine, Lund University. 64 p.

Research output: ThesisDoctoral Thesis (compilation)

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