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Organization of mitochondrial gene expression in two distinctribosome-containing assemblies
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Mitochondria contain their own genetic system that provides subunits of the complexesdriving oxidative phosphorylation. A quarter of the mitochondrial proteome participates ingene expression, but how all these factors are orchestrated and spatially organized is currentlyunknown. Here we developed a novel method to purify native complexes of mitochondrialribosomes. Quantitative mass-spectrometry revealed extensive interactions of ribosomes withfactors that represent all the steps of post-transcriptional gene expression. These interactionsresult in large expressosomes-like assemblies that we termed MIOREX (MItochondrialORganization of gene EXpression) complexes. Most MIOREX complexes are evenlydistributed throughout the mitochondrial network, while a subset is present as nucleoid-MIOREX complexes that unite the whole spectrum of organellar gene expression. Our worktherefore provides a novel conceptual framework for the spatial organization of mitochondrialprotein synthesis that likely developed to facilitate gene expression in the organelle.

National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:su:diva-107645OAI: oai:DiVA.org:su-107645DiVA: diva2:748890
Available from: 2014-09-22 Created: 2014-09-22 Last updated: 2014-09-23Bibliographically approved
In thesis
1. Organization of mitochondrial gene expression in yeast: Specific features of organellar protein synthesis
Open this publication in new window or tab >>Organization of mitochondrial gene expression in yeast: Specific features of organellar protein synthesis
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2014. 73 p.
Keyword
Mitochondria, translation, bc1 complex, ribosome, gene expression
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-107568 (URN)978-91-7447-985-0 (ISBN)
Public defence
2014-11-07, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
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Note

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

Available from: 2014-10-16 Created: 2014-09-19 Last updated: 2014-11-10Bibliographically approved

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