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Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation
Vise andre og tillknytning
2010 (engelsk)Inngår i: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 21, nr 12, s. 1937-1944Artikkel i tidsskrift, Editorial material (Annet vitenskapelig) Published
Abstract [en]

Biogenesis of respiratory chain complexes depends on the expression of mitochondrial-encoded subunits. Their synthesis occurs on membrane-associated ribosomes and is probably coupled to their membrane insertion. Defects in expression of mitochondrial translation products are among the major causes of mitochondrial disorders. Mdm38 is related to Letm1, a protein affected in Wolf-Hirschhorn syndrome patients. Like Mba1 and Oxa1, Mdm38 is an inner membrane protein that interacts with ribosomes and is involved in respiratory chain biogenesis. We find that simultaneous loss of Mba1 and Mdm38 causes severe synthetic defects in the biogenesis of cytochrome reductase and cytochrome oxidase. These defects are not due to a compromised membrane binding of ribosomes but the consequence of a mis-regulation in the synthesis of Cox1 and cytochrome b. Cox1 expression is restored by replacing Cox1-specific regulatory regions in the mRNA. We conclude, that Mdm38 and Mba1 exhibit overlapping regulatory functions in translation of selected mitochondrial mRNAs.

sted, utgiver, år, opplag, sider
2010. Vol. 21, nr 12, s. 1937-1944
HSV kategori
Identifikatorer
URN: urn:nbn:se:su:diva-107644DOI: 10.1091/mbc.E10-02-0101ISI: 000278681700003OAI: oai:DiVA.org:su-107644DiVA, id: diva2:748884
Tilgjengelig fra: 2014-09-22 Laget: 2014-09-22 Sist oppdatert: 2017-12-05bibliografisk kontrollert
Inngår i avhandling
1. Organization of mitochondrial gene expression in yeast: Specific features of organellar protein synthesis
Åpne denne publikasjonen i ny fane eller vindu >>Organization of mitochondrial gene expression in yeast: Specific features of organellar protein synthesis
2014 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Mitochondria contain their own genetic system, encoding key subunits of the oxidative phosphorylation system. These subunits are expressed by an organelle-specific gene expression machinery. This work revealed a number of fundamental aspects of mitochondrial gene expression and provides evidence that this process is organized in a unique and organelle-specific manner which likely evolved to optimize protein synthesis and assembly in mitochondria. Most importantly, improving the experimental handling of ribosomes we could show that mitochondrial ribosomes are organized in large assemblies that we termed MIOREX complexes. Ribosomes present in these complexes organize gene expression by recruiting multiple factors required for post-transcriptional steps. In addition, we could reveal mechanisms by which ribosome-interactor complexes modulate and coordinate the expression and assembly of the respiratory chain subunits. For example we showed that the Cbp3-Cbp6 complex binds to the ribosome in proximity to the tunnel exit to coordinate synthesis and assembly of cytochrome b. This location perfectly positions Cbp3-Cbp6 for direct binding to newly synthesized cytochrome b and permits Cbp3-Cbp6 to establish a feedback loop that allows modulation of cytochrome b synthesis in response to assembly efficiency. Likewise the interaction of the membrane-anchor proteins Mba1 and Mdm38 with the tunnel exit region enables them to participate in the translation of the two intron-encoding genes COX1 and COB in addition to their role in membrane insertion.  In summary, work presented in this thesis shows that mitochondrial gene expression is a highly organized and regulated process. The concepts and technical innovations will facilitate the elucidation of many additional and important aspects and therefore contribute to the general understanding of how proteins are synthesized in mitochondria.

sted, utgiver, år, opplag, sider
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2014. s. 73
Emneord
Mitochondria, translation, bc1 complex, ribosome, gene expression
HSV kategori
Forskningsprogram
biokemi
Identifikatorer
urn:nbn:se:su:diva-107568 (URN)978-91-7447-985-0 (ISBN)
Disputas
2014-11-07, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (engelsk)
Opponent
Veileder
Merknad

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Tilgjengelig fra: 2014-10-16 Laget: 2014-09-19 Sist oppdatert: 2018-08-28bibliografisk kontrollert

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