A mouse model of mitochondrial complex III dysfunction induced by myxothiazol.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4379814
- author
- Davoudi, Mina
LU
; Kallijärvi, Jukka LU ; Marjavaara, Sanna ; Kotarsky, Heike LU ; Hanson, Eva ; Levéen, Per LU and Fellman, Vineta LU
- organization
- publishing date
- 2014
- 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
- pmid:24661880
- 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
- 2016-04-01 11:01:04
- date last changed
- 2022-03-27 21:43:58
@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}}, doi = {{10.1016/j.bbrc.2014.03.058}}, volume = {{446}}, year = {{2014}}, }