COX7A2L/SCAFI and Pre-Complex III Modify Respiratory Chain Supercomplex Formation in Different Mouse Strains with a Bcs1/Mutation

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dc.contributor University of Helsinki, Children's Hospital en
dc.contributor.author Davoudi, Mina
dc.contributor.author Kotarsky, Heike
dc.contributor.author Hansson, Eva
dc.contributor.author Kallijarvi, Jukka
dc.contributor.author Fellman, Vineta
dc.date.accessioned 2017-03-07T09:27:01Z
dc.date.available 2017-03-07T09:27:01Z
dc.date.issued 2016-12-20
dc.identifier.citation Davoudi , M , Kotarsky , H , Hansson , E , Kallijarvi , J & Fellman , V 2016 , ' COX7A2L/SCAFI and Pre-Complex III Modify Respiratory Chain Supercomplex Formation in Different Mouse Strains with a Bcs1/Mutation ' , PLoS One , vol. 11 , no. 12 , 0168774 . https://doi.org/10.1371/journal.pone.0168774 en
dc.identifier.issn 1932-6203
dc.identifier.other PURE: 80898961
dc.identifier.other PURE UUID: 41f8f9a7-26ec-44ed-a85a-19f3bcd7982d
dc.identifier.other WOS: 000392842900075
dc.identifier.other Scopus: 85006900497
dc.identifier.uri http://hdl.handle.net/10138/176778
dc.description.abstract The COX7A2L (Supercomplex Assembly Factor I, SCAFI) protein has been proposed to be a mitochondrial supercomplex assembly factor required for respirasome (supercomplex containing complexes I, III, and IV) formation. In the C57BU6 mouse strain a homozygous in-frame 6-base-pair deletion in the COX7a2I/SCAF1 gene resulting in unstable protein and suggesting loss of function was previously identified. The loss of SCAFI was shown to impede respirasome formation, a major concern for the use of C57BL mouse strains in mitochondrial research. In contradiction, another recent study suggested that supercomplex formation is independent of SCAFI isoforms. We investigated whether SCAFI isoform status affected the disease severity and supercomplex formation in the liver of Bcs1a232A>G knock-in mice with incomplete complex III assembly. In homozygotes (Bcs1/(G/G)) of mixed (C57BL/6:129/Sv) genetic background, the lifespan was similar in mice with wild-type SCAFI allele and in those homozygous (SCAF/(short/short)) for the deleted SCAF1 variant (34 3 days; n = 6 vs. 32 +/- 2 days; n = 7, respectively). SCAFI heterozygosity (SCAF/(long/short)) resulted in decreased SCAFI protein but respirasome assembly was unaffected. Congenic (C57BL/6) mice were of the genotype SCAF(short/short) and had no detectable SCAFI protein. In their liver mitochondria, respirasome composition was altered as compared to mixed background mice. Complex IV was mainly present as monomers and dimers, and only low amounts were found in combination with complex I and complex III or with precomplex III. The main supercomplex in the liver mitochondria of C57BU6 mice comprised only complexes I and III. In conclusion, in liver mitochondria of C57BL/6 mice, supercomplexes had markedly reduced amount of, but were not completely depleted of, complex IV, supporting a role for COX7A2L/SCAFI in supercomplex assembly. However, the disease progression of the Bcs1/mutant mice was unrelated to SCAFI isoforms and supercomplex composition, suggesting that other genetic factors contribute to the different survival in the different genetic backgrounds. en
dc.format.extent 11
dc.language.iso eng
dc.relation.ispartof PLoS One
dc.rights en
dc.subject PROTEIN en
dc.subject MITOCHONDRIA en
dc.subject RCF1 en
dc.subject 3111 Biomedicine en
dc.title COX7A2L/SCAFI and Pre-Complex III Modify Respiratory Chain Supercomplex Formation in Different Mouse Strains with a Bcs1/Mutation en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1371/journal.pone.0168774
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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