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Investigating the Role of ROMO1 in Mitochondrial Protein Import and Inner Membrane Morphology

dc.contributor.advisorRehling, Peter Prof. Dr.
dc.contributor.authorRichter, Frank
dc.titleInvestigating the Role of ROMO1 in Mitochondrial Protein Import and Inner Membrane Morphologyde
dc.contributor.refereeRehling, Peter Prof. Dr.
dc.description.abstractengMitochondria are vital organelles that perform fundamental functions such as ATP synthesis and  iron-sulfur cluster formation. More than 99% of the mitochondrial proteome is imported by dedicated translocation machineries. Proteins destined for the mitochondrial matrix, or the inner membrane, are imported by the presequence translocase of the inner membrane (TIM23 complex). The molecular architecture of the mitochondrial translocation machinery is conserved between yeast and human, but most of the functional characterization to date has been carried out in S.cerevisiae.  Quantitative mass spectrometry was used to analyze the interactome of the isolated human TIM23 complex. A high enrichment of a protein named ROMO1 was found. The upregulation of ROMO1 had previously been correlated with high levels of reactive oxygen species (ROS). It also plays a role in the regulation of mitochondrial morphology. However, the molecular function of ROMO1 is unknown. ROMO1 displays sequence similarity to yeast Mgr2, which is a subunit of the TIM23 complex and acts in quality control during import. Using HEK293T cells as a model system, this study showed, by immunoprecipitation, that ROMO1 interacts with TIM21 and TIM23 and is therefore a constituent of the human TIM23 complex. To study the function of ROMO1, a CRISPR/Cas9-mediated knockout cell line was generated, which displays aberrant cristae structure. Biochemical analysis showed that the processing of OPA1, a protein involved in mitochondrial morphology, is disturbed. Furthermore, steady-state levels of the OPA1 processing protease, YME1L, are reduced. Even though ROMO1 couples TIM21 onto TIM23 and affects respiratory chain assembly, general protein import is not dependent on ROMO1. However, in vitro import assays showed that the import of YME1L is drastically affected in the absence of ROMO1. The molecular reason for this import defect seems to be the unusually long targeting sequence of YME1L. Therefore, an interesting link between protein import and inner membrane morphology could be
dc.contributor.coRefereeJakobs, Stefan Prof. Dr.
dc.subject.engProtein Importde
dc.affiliation.instituteBiologische Fakultät für Biologie und Psychologiede
dc.subject.gokfullBiologie (PPN619462639)de

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