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dc.contributor.advisor Rehling, Peter Prof. Dr. de
dc.contributor.author Alkhaja, Alwaleed de
dc.date.accessioned 2012-06-07T18:35:01Z de
dc.date.accessioned 2013-01-18T14:26:57Z de
dc.date.available 2013-01-30T23:51:05Z de
dc.date.issued 2012-06-07 de
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-000D-F0B5-6 de
dc.format.mimetype application/pdf de
dc.language.iso eng de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ de
dc.title The identification and characterization of Mio10 and MINOS1 as novel regulators of mitochondrial inner membrane organization de
dc.type doctoralThesis de
dc.title.translated The identification and characterization of Mio10 and MINOS1 as novel regulators of mitochondrial inner membrane organization de
dc.contributor.referee Rehling, Peter Prof. Dr. de
dc.date.examination 2012-05-02 de
dc.subject.dnb 570 Biowissenschaften de
dc.subject.dnb Biologie de
dc.subject.gok WF 200 de
dc.description.abstracteng Various mitochondrial inner membrane proteins contribute to the structure of cristae membranes and to the overall dynamic morphology of the inner membrane. These proteins include the F1FOATPase dimers, which contribute to the curvature and angular shape of cristae. Also, Fcj1/Mitofilin are involved in cristae junction formation and act in an antagonistic manner in inner membrane curvature with respect to F1FOATPase dimers. Whereas several small proteins mediate F1FOATPase dimerization in yeast by binding sequentially at monomer interfaces, the exact nature of what promotes F1FOATPase dimerization in higher eukaryotes is yet to be determined. To this end, the initial aim of this study was to identify novel F1FOATPase dimerization factors in higher eukaryotes that parallel the action of small dimerization factors in yeast. An in silico approach to identify novel F1FOATPase dimerization factors resulted in the identification of the human mitochondrial protein MINOS1 as a potential candidate. MINOS1, along with its human homolog, Mio10, were investigated. These proteins however were found not to be stably associated with the F1FOATPase. Moreover, Mio10 did not affect F1FOATPase dimerization, oligomerization, or enzymatic activity. Thus a role of Mio10 and MINOS in dimerization was excluded. Instead by using an affinity purification based mass spectrometric analysis, Mio10/MINOS1 were identified as novel interaction partners of Fcj1/Mitofilin. Topological analysis of Mio10 and MINOS together with results of size exclusion chromatography indicated that the two proteins form large mitochondrial inner membrane complexes. Furthermore, analysis of a MIO10 deletion strain by fluorescence and electron microscopy provided evidence for the critical role that Mio10 plays in inner membrane organization. Mitochondria from mio10∆ and fcj1∆ strains exhibited leaflet-like stacked cristae membranes and appeared to have lost defined cristae tips. The complex that contains Mio10/Fcj1 in yeast and MINOS1/Mitofilin in human mitochondria was hence termed as the MINOS complex (Mitochondrial Inner membrane Organizing System). The presented findings highlight the functional and evolutionary significance of the MINOS complex as a player in mitochondrial inner membrane architecture as well as a multifunctional component in eukaryotic mitochondria and potentially in other cellular organelles. de
dc.contributor.coReferee Jahn, Reinhard Prof. Dr. de
dc.contributor.thirdReferee Zweckstetter, Markus Prof. Dr. de
dc.subject.topic Göttingen Graduate School for Neurosciences and Molecular Biosciences (GGNB) de
dc.subject.ger Mitochondrien innere Membran Morphologie MINOS Organisation de
dc.subject.eng Mitochondria Inner membrane morphology MINOS organization de
dc.subject.bk 42 de
dc.identifier.urn urn:nbn:de:gbv:7-webdoc-3546-2 de
dc.identifier.purl webdoc-3546 de
dc.affiliation.institute Göttinger Graduiertenschule für Neurowissenschaften und Molekulare Biowissenschaften (GGNB) de
dc.identifier.ppn 725573759 de

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