The identification and characterization of Mio10 and MINOS1 as novel regulators of mitochondrial inner membrane organization

Alkhaja, Alwaleed

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.identifier.uri	http://dx.doi.org/10.53846/goediss-3260
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3260
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3260
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

Dateien

Name:alkhaja.pdf

Größe:32.85Mb

Format:PDF

Öffnen

Name:: alkhaja.pdf
Größe:: 32.85Mb
Format:: PDF

Öffnen

Das Dokument erscheint in:

GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1115]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

Zur Kurzanzeige