• Deutsch
    • English
  • English 
    • Deutsch
    • English
  • Login
Item View 
  •   Home
  • Medizin
  • Molekulare Medizin
  • Item View
  •   Home
  • Medizin
  • Molekulare Medizin
  • Item View
JavaScript is disabled for your browser. Some features of this site may not work without it.

Analysis of the role of Cox20 during the early steps of Cox2 biogenesis

by Isotta Lorenzi
Doctoral thesis
Date of Examination:2016-03-18
Date of issue:2016-08-24
Advisor:Prof. Dr. Peter Rehling
Referee:Prof. Dr. Peter Rehling
Referee:Prof. Dr. Ralph Kehlenbach
crossref-logoPersistent Address: http://dx.doi.org/10.53846/goediss-5824

 

 

Files in this item

Name:PhD-thesis-I-Lorenzi-publication.pdf
Size:28.5Mb
Format:PDF
ViewOpen

The following license files are associated with this item:


Abstract

English

The catalytic core of the cytochrome c oxidase (complex IV), the terminal enzyme of the mitochondrial respiratory chain, comprises three mitochondria-encoded subunits Cox1, Cox2 and Cox3 that are highly conserved among species. Cytochrome c oxidase maturation is a coordinated process requiring specialized assembly factors that assist in the sequential formation of sub-complexes, also termed assembly intermediates. In recent decades, fruitful research of complex IV biogenesis, in the yeast S. cerevisiae, has revealed that Cox2 is inserted into the inner mitochondrial membrane via a co-translational mechanism. This is facilitated by the mitochondrial ribosome binding protein Mba1 and the Oxa1 insertase. Following insertion, various assembly factors, such as Cox20, are required for the maturation of Cox2. However, the mechanism by which insertion and assembly are coordinated is not well understood. The Cox20 protein is a ubiquitous Cox2-chaperone, involved in Cox2 Nterminal processing. In human, Cox2 is expressed without N-terminal peptide, suggesting an additional role of Cox20 beyond its processing function. In fact, a patient mutation in the Cox20 human homolog leads to impaired cytochrome c oxidase assembly. Results presented in this thesis elucidate the molecular role of Cox20 in the early steps of Cox2 biogenesis. For this purpose, a mass spectrometry analysis using a SILAC approach was undertaken to identify novel Cox20 interacting partners. Analysis of the composition of Cox20-containing complexes revealed proteins involved in Cox2 translation, membrane insertion and metallation. For the first time, the identified interaction with the mitochondrial ribosome provides a new link of Cox20 function to Cox2 synthesis. Furthermore, functional analysis of the novel Cox20-Mba1 complex suggested a novel role of Mba1 with regard to Cox2 maturation. The presented data propose a new shuttling mechanism of newly translated Cox2 from the ribosome and the insertion machinery to maturing mitochondrial assembly intermediates.
Keywords: Ribosome; Cytochrome c oxidase; Mitochondria; Cox2; Respiratory chain
 

Statistik

Publish here

Browse

All of eDissFaculties & ProgramsIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesTypeThis FacultyIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesType

Help & Info

Publishing on eDissPDF GuideTerms of ContractFAQ

Contact Us | Impressum | Cookie Consents | Data Protection Information
eDiss Office - SUB Göttingen (Central Library)
Platz der Göttinger Sieben 1
Mo - Fr 10:00 – 12:00 h


Tel.: +49 (0)551 39-27809 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
ediss_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]
Göttingen State and University Library | Göttingen University
Medicine Library (Doctoral candidates of medicine only)
Robert-Koch-Str. 40
Mon – Fri 8:00 – 24:00 h
Sat - Sun 8:00 – 22:00 h
Holidays 10:00 – 20:00 h
Tel.: +49 551 39-8395 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
bbmed_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]