@phdthesis{Ott2013,
  author    = {Ott, Christine Kornelia},
  title     = {Diverse Aspects of the Sorting and Assembly Machinery in Human Mitochondria},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85462},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Mitochondria are organelles of endosymbiotic origin, which play many important roles in eukaryotic cells. Mitochondria are surrounded by two membranes and, considering that most of the mitochondrial proteins are produced in the cytosol, possess import machineries, which transport mitochondria-targeted proteins to their designated location. A special class of outer mitochondrial membrane (OMM) proteins, the β-barrel proteins, require the sorting and assembly machinery (SAM) for their OMM integration. Both mitochondrial β-barrel proteins and the central component of the SAM complex, Sam50, have homologs in gram-negative bacteria. In yeast mitochondria, bacterial β-barrel proteins can be imported and assembled into the OMM. Our group demonstrated that this, however, is not the case for human mitochondria, which import only neisserial β barrel proteins, but not those of Escherichia coli and Salmonella enterica. As a part of this study, I could demonstrate that β-barrel proteins such as Omp85 and PorB of different Neisseria species are targeted to human mitochondria. Interestingly, only proteins belonging to the neisserial Omp85 family were integrated into the OMM, whereas PorB was imported into mitochondria but not assembled. By exchanging parts of homologous neisserial Omp85 and E. coli BamA and, similarly, of neisserial PorB and E. coli OmpC, it could be demonstrated in this work that the mitochondrial import signal of bacterial β barrel proteins cannot be limited to one short linear sequence, but rather secondary structure and protein charge seem to play an important role, as well as specific residues in the last β-strand of Omp85. Omp85 possesses five conserved POTRA domains in its amino-terminal part. This work additionally demonstrated that in human mitochondria, at least two POTRA domains of Omp85 are necessary for membrane integration and functionality of Omp85. In the second part of this work, the influence of Sam50 on the mitochondrial cristae structure was investigated. This work contributed to a study performed by our group in which it was confirmed that Sam50 is present in a high molecular weight complex together with mitofilin, CHCHD3, CHCHD6, DnaJC11, metaxin 1 and metaxin 2. This connection between the inner and outer mitochondrial membrane was shown to be crucial for the maintenance of the mitochondrial cristae structure. In addition, a role of Sam50 in respiratory complex assembly, suggested by a SILAC experiment conducted in our group, could be confirmed by in vitro import studies. An influence of Sam50 not only on respiratory complexes but also on the recently described respiratory complex assembly factor TTC19 was demonstrated. It was shown that TTC19 not only plays a role in complex III assembly as published, but also influences the assembly of respiratory complex IV. Thus, in this part of the work a connection between the OMM protein Sam50 and maintenance of cristae structure, respiratory complex assembly and an assembly factor could be established.},
  subject      = {Mitochondrien},
  language  = {en}
}
@article{Kozjak‑PavlovicOttUtechetal.2013,
  author    = {Kozjak‑Pavlovic, Vera and Ott, Christine and Utech, Mandy and Goetz, Monika and Rudel, Thomas},
  title     = {Requirements for the import of neisserial Omp85 into the outer membrane of human mitochondria},
  series = {Bioscience Reports},
  journal   = {Bioscience Reports},
  doi       = {10.1042/BSR20130007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96381},
  year      = {2013},
  abstract  = {β-Barrel proteins are present only in the outer membranes of Gram-negative bacteria, chloroplasts and mitochondria. Fungal mitochondria were shown to readily import and assemble bacterial β-barrel proteins, but human mitochondria exhibit certain selectivity. Whereas enterobacterial β-barrel proteins are not imported, neisserial ones are. Of those, solely neisserial Omp85 is integrated into the outer membrane of mitochondria. In this study, we wanted to identify the signal that targets neisserial β-barrel proteins to mitochondria. We exchanged parts of neisserial Omp85 and PorB with their Escherichia coli homologues BamA and OmpC. For PorB, we could show that its C-terminal quarter can direct OmpC to mitochondria. In the case of Omp85, we could identify several amino acids of the C-terminal β-sorting signal as crucial for mitochondrial targeting. Additionally, we found that at least two POTRA (polypeptide-transport associated) domains and not only the β-sorting signal of Omp85 are needed for its membrane integration and function in human mitochondria. We conclude that the signal that directs neisserial β-barrel proteins to mitochondria is not conserved between these proteins. Furthermore, a linear mitochondrial targeting signal probably does not exist. It is possible that the secondary structure of β-barrel proteins plays a role in directing these proteins to mitochondria.},
  language  = {en}
}