Show simple item record

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

dc.contributor.advisorRehling, Peter Prof.
dc.contributor.authorAlkhaja, Alwaleedde
dc.titleThe identification and characterization of Mio10 and MINOS1 as novel regulators of mitochondrial inner membrane organizationde
dc.title.translatedThe identification and characterization of Mio10 and MINOS1 as novel regulators of mitochondrial inner membrane organizationde
dc.contributor.refereeRehling, Peter Prof.
dc.subject.dnb570 Biowissenschaftende
dc.subject.gokWF 200de
dc.description.abstractengVarious 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
dc.contributor.coRefereeJahn, Reinhard Prof.
dc.contributor.thirdRefereeZweckstetter, Markus Prof.
dc.subject.topicGöttingen Graduate School for Neurosciences and Molecular Biosciences (GGNB)de
dc.subject.gerMitochondrien innere Membran Morphologie MINOS Organisationde
dc.subject.engMitochondria Inner membrane morphology MINOS organizationde
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften und Molekulare Biowissenschaften (GGNB)de

Files in this item


This item appears in the following Collection(s)

Show simple item record