| dc.contributor.advisor | Rehling, Peter Prof. Dr. | |
| dc.contributor.author | Wang, Cong | |
| dc.date.accessioned | 2020-12-02T14:22:38Z | |
| dc.date.available | 2020-12-02T14:22:38Z | |
| dc.date.issued | 2020-12-02 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0005-1509-A | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-8330 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-8330 | |
| dc.language.iso | eng | de |
| dc.relation.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 572 | de |
| dc.title | Investigation of early assembly of OXPHOS complexes during mitochondrial translation | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Bohnsack, Markus Prof. Dr. | |
| dc.date.examination | 2018-09-14 | |
| dc.description.abstracteng | After a long time of coevolution between mitochondria and their eukaryotic
host cells, the mitochondrial genome has diverged severely from it’s α-
proteobacterial ancestors. Mitochondrial genes have mainly been transferred
to the cytosolic genome and only a small number of highly hydrophobic core
subunits of the oxidative phosphorylation system (OXPHOS) have been
retained within the mitochondrial genome.
Since the OXPHOS consist of subunits of both mitochondrial and cytosolic
origins, the translation of mitochondrial proteins has to be coordinated with the
translation and import of proteins translated on cytosolic ribosomes to provide
efficient assembly of the OXPHOS subunits.
One mechanism to regulate mitochondrial translation by cytosolic events is
via regulators for mitochondrial translation. Such proteins are present during
mitochondrial translation and can either interact with mitochondrial mRNAs, or
associate with the mitochondrial ribosome. Even though many mitochondrial
translation regulators are well characterized in yeast, little is known about
them in human mitochondria.
In this thesis, I was able to isolate the ribosome-associated early assembly
intermediate of the cytochrome c oxidase, MITRAC, during the translation of
COX1. Western blot and mass spectrometry analysis showed the presence of
the insertase OXA1L within this complex and cryoEM analysis could localize
the complex near the exit tunnel of the mitochondrial ribosome.
In a second part, MITRAC15, which was characterized as a MITRAC subunit
and a subunit of the PP-b early assembly intermediate, was functionally
characterized. MITRAC15 could be shown to be a positive translation
regulator of ND2 and is the first identified protein to possibly copurify with
nascent chains of mitochondrial complex I proteins after puromycin treatment.
Furthermore, it was shown that MITRAC15 is able to stall the assembly of the
cytochrome c oxidase and therefore, links complex I and IV biogenesis. | de |
| dc.contributor.coReferee | Urlaub, Henning Prof. Dr. | |
| dc.contributor.thirdReferee | Stark, Holger Prof. Dr. | |
| dc.contributor.thirdReferee | Jakobs, Stefan Prof. Dr. | |
| dc.contributor.thirdReferee | Stein, Alexander Dr. | |
| dc.subject.eng | Mitochondria | de |
| dc.subject.eng | OXPHOS | de |
| dc.subject.eng | complex IV | de |
| dc.subject.eng | complex I | de |
| dc.subject.eng | Mitochondrial translation | de |
| dc.subject.eng | Translation regulation | de |
| dc.subject.eng | Human | de |
| dc.subject.eng | Structure | de |
| dc.subject.eng | MITRAC | de |
| dc.subject.eng | Ribosome | de |
| dc.subject.eng | C12ORF62 | de |
| dc.subject.eng | MITRAC15 | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-1509-A-4 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 1741829925 | |