Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Organization of mitochondrial gene expression in yeast: Specific features of organellar protein synthesis
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. (Martin Ott)
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 [en]
Mitochondria, translation, bc1 complex, ribosome, gene expression
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:su:diva-107568ISBN: 978-91-7447-985-0 (print)OAI: oai:DiVA.org:su-107568DiVA: diva2:748903
Public defence
2014-11-07, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
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
List of papers
1. Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation
Open this publication in new window or tab >>Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation
Show others...
2010 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 21, no 12, 1937-1944 p.Article in journal, Editorial material (Other academic) 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.

National Category
Cell Biology
Identifiers
urn:nbn:se:su:diva-107644 (URN)10.1091/mbc.E10-02-0101 (DOI)000278681700003 ()
Available from: 2014-09-22 Created: 2014-09-22 Last updated: 2017-12-05Bibliographically approved
2. Cbp3-Cbp6 interacts with the yeast mitochondrial ribosomal tunnel exit and promotes cytochrome b synthesis and assembly
Open this publication in new window or tab >>Cbp3-Cbp6 interacts with the yeast mitochondrial ribosomal tunnel exit and promotes cytochrome b synthesis and assembly
Show others...
2011 (English)In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 193, no 6, 1101-1114 p.Article in journal (Refereed) Published
Abstract [en]

Mitochondria contain their own genetic system to express a small number of hydrophobic polypeptides, including cytochrome b, an essential subunit of the bc(1) complex of the respiratory chain. In this paper, we show in yeast that Cbp3, a bc(1) complex assembly factor, and Cbp6, a regulator of cytochrome b translation, form a complex that associates with the polypeptide tunnel exit of mitochondrial ribosomes and that exhibits two important functions in the biogenesis of cytochrome b. On the one hand, the interaction of Cbp3 and Cbp6 with mitochondrial ribosomes is necessary for efficient translation of cytochrome b messenger ribonucleic acid or transcript. On the other hand, the Cbp3-Cbp6 complex interacts directly with newly synthesized cytochrome b in an assembly intermediate that is not ribosome bound and that contains the assembly factor Cbp4. Our results suggest that synthesis of cytochrome b occurs preferentially on those ribosomes that have the Cbp3-Cbp6 complex bound to their tunnel exit, an arrangement that may ensure tight coordination of cytochrome b synthesis and assembly.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-67580 (URN)10.1083/jcb.201103132 (DOI)000291586400014 ()
Note
authorCount :8Available from: 2011-12-29 Created: 2011-12-29 Last updated: 2017-12-08Bibliographically approved
3. The Cbp3-Cbp6 complex coordinates cytochrome b synthesis with bc(1) complex assembly in yeast mitochondria
Open this publication in new window or tab >>The Cbp3-Cbp6 complex coordinates cytochrome b synthesis with bc(1) complex assembly in yeast mitochondria
Show others...
2012 (English)In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 199, no 1, 137-150 p.Article in journal (Refereed) Published
Abstract [en]

Respiratory chain complexes in mitochondria are assembled from subunits derived from two genetic systems. For example, the bc1 complex consists of nine nuclear encoded subunits and the mitochondrially encoded subunit cytochrome b. We recently showed that the Cbp3-Cbp6 complex has a dual function for biogenesis of cytochrome b: it is both required for efficient synthesis of cytochrome b and for protection of the newly synthesized protein from proteolysis. Here, we report that Cbp3-Cbp6 also coordinates cytochrome b synthesis with bc1 complex assembly. We show that newly synthesized cytochrome b assembled through a series of four assembly intermediates. Blocking assembly at early and intermediate steps resulted in sequestration of Cbp3-Cbp6 in a cytochrome b-containing complex, thereby making Cbp3-Cbp6 unavailable for cytochrome b synthesis and thus reducing overall cytochrome b levels. This feedback loop regulates protein synthesis at the inner mitochondrial membrane by directly monitoring the efficiency of bc1 complex assembly.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-81049 (URN)10.1083/jcb.201206040 (DOI)000309524500015 ()
Available from: 2012-10-08 Created: 2012-10-08 Last updated: 2017-12-07Bibliographically approved
4. Organization of mitochondrial gene expression in two distinctribosome-containing assemblies
Open this publication in new window or tab >>Organization of mitochondrial gene expression in two distinctribosome-containing assemblies
Show others...
(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:nbn:se:su:diva-107645 (URN)
Available from: 2014-09-22 Created: 2014-09-22 Last updated: 2014-09-23Bibliographically approved

Open Access in DiVA

Dissertation Kehrein(1329 kB)245 downloads
File information
File name FULLTEXT01.pdfFile size 1329 kBChecksum SHA-512
d4fee7b36e2577b2dd2287b4992256238fa4bcfe8611b2fa490948d62fe023c714545c316bf1da39fa62d1c45894aac9601fa1bdd05dccd3e3e384f38ef40855
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Kehrein, Kirsten
By organisation
Department of Biochemistry and Biophysics
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 245 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 213 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf