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Complex I Function and Supercomplex Formation Are Preserved in Liver Mitochondria Despite Progressive Complex III Deficiency.

Davoudi, Mina LU ; Kotarsky, Heike LU ; Hansson, Eva LU and Fellman, Vineta LU (2014) In PLoS ONE 9(1).
Abstract
Functional oxidative phosphorylation requires appropriately assembled mitochondrial respiratory complexes and their supercomplexes formed mainly of complexes I, III and IV. BCS1L is the chaperone needed to incorporate the catalytic subunit, Rieske iron-sulfur protein, into complex III at the final stage of its assembly. In cell culture studies, this subunit has been considered necessary for supercomplex formation and for maintaining the stability of complex I. Our aim was to assess the importance of fully assembled complex III for supercomplex formation in intact liver tissue. We used our transgenic mouse model with a homozygous c.232A>G mutation in Bcs1l leading to decreased expression of BCS1L and progressive decrease of Rieske... (More)
Functional oxidative phosphorylation requires appropriately assembled mitochondrial respiratory complexes and their supercomplexes formed mainly of complexes I, III and IV. BCS1L is the chaperone needed to incorporate the catalytic subunit, Rieske iron-sulfur protein, into complex III at the final stage of its assembly. In cell culture studies, this subunit has been considered necessary for supercomplex formation and for maintaining the stability of complex I. Our aim was to assess the importance of fully assembled complex III for supercomplex formation in intact liver tissue. We used our transgenic mouse model with a homozygous c.232A>G mutation in Bcs1l leading to decreased expression of BCS1L and progressive decrease of Rieske iron-sulfur protein in complex III, resulting in hepatopathy. We studied supercomplex formation at different ages using blue native gel electrophoresis and complex activity using high-resolution respirometry. In isolated liver mitochondria of young and healthy homozygous mutant mice, we found similar supercomplexes as in wild type. In homozygotes aged 27-29 days with liver disorder, complex III was predominantly a pre-complex lacking Rieske iron-sulfur protein. However, the main supercomplex was clearly detected and contained complex III mainly in the pre-complex form. Oxygen consumption of complex IV was similar and that of complex I was twofold compared with controls. These complexes in free form were more abundant in homozygotes than in controls, and the mRNA of complex I subunits were upregulated. In conclusion, when complex III assembly is deficient, the pre-complex without Rieske iron-sulfur protein can participate with available fully assembled complex III in supercomplex formation, complex I function is preserved, and respiratory chain stability is maintained. (Less)
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published
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in
PLoS ONE
volume
9
issue
1
publisher
Public Library of Science
external identifiers
  • pmid:24466228
  • wos:000330283100210
  • scopus:84899481277
ISSN
1932-6203
DOI
10.1371/journal.pone.0086767
language
English
LU publication?
yes
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305d1ae5-df6b-432a-8666-d300675bd143 (old id 4290586)
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http://www.ncbi.nlm.nih.gov/pubmed/24466228?dopt=Abstract
date added to LUP
2014-02-07 11:59:38
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2017-08-13 03:50:28
@article{305d1ae5-df6b-432a-8666-d300675bd143,
  abstract     = {Functional oxidative phosphorylation requires appropriately assembled mitochondrial respiratory complexes and their supercomplexes formed mainly of complexes I, III and IV. BCS1L is the chaperone needed to incorporate the catalytic subunit, Rieske iron-sulfur protein, into complex III at the final stage of its assembly. In cell culture studies, this subunit has been considered necessary for supercomplex formation and for maintaining the stability of complex I. Our aim was to assess the importance of fully assembled complex III for supercomplex formation in intact liver tissue. We used our transgenic mouse model with a homozygous c.232A>G mutation in Bcs1l leading to decreased expression of BCS1L and progressive decrease of Rieske iron-sulfur protein in complex III, resulting in hepatopathy. We studied supercomplex formation at different ages using blue native gel electrophoresis and complex activity using high-resolution respirometry. In isolated liver mitochondria of young and healthy homozygous mutant mice, we found similar supercomplexes as in wild type. In homozygotes aged 27-29 days with liver disorder, complex III was predominantly a pre-complex lacking Rieske iron-sulfur protein. However, the main supercomplex was clearly detected and contained complex III mainly in the pre-complex form. Oxygen consumption of complex IV was similar and that of complex I was twofold compared with controls. These complexes in free form were more abundant in homozygotes than in controls, and the mRNA of complex I subunits were upregulated. In conclusion, when complex III assembly is deficient, the pre-complex without Rieske iron-sulfur protein can participate with available fully assembled complex III in supercomplex formation, complex I function is preserved, and respiratory chain stability is maintained.},
  articleno    = {e86767},
  author       = {Davoudi, Mina and Kotarsky, Heike and Hansson, Eva and Fellman, Vineta},
  issn         = {1932-6203},
  language     = {eng},
  number       = {1},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Complex I Function and Supercomplex Formation Are Preserved in Liver Mitochondria Despite Progressive Complex III Deficiency.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0086767},
  volume       = {9},
  year         = {2014},
}