@article{IoakeimidisOttKozjakPavlovicetal.2014,
  author    = {Ioakeimidis, Fotis and Ott, Christine and Kozjak-Pavlovic, Vera and Violitzi, Foteini and Rinotas, Vagelis and Makrinou, Eleni and Eliopoulos, Elias and Fasseas, Costas and Kollias, George and Douni, Eleni},
  title     = {A Splicing Mutation in the Novel Mitochondrial Protein DNAJC11 Causes Motor Neuron Pathology Associated with Cristae Disorganization, and Lymphoid Abnormalities in Mice},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0104237},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115581},
  pages     = {e104237},
  year      = {2014},
  abstract  = {Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co-immunoprecipitates with proteins of the mitochondrial contact site (MICOS) complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases.},
  language  = {en}
}
@article{KatoLuRapaportetal.2013,
  author    = {Kato, Hiroki and Lu, Qiping and Rapaport, Doron and Kozjak-Pavlovic, Vera},
  title     = {Tom70 Is Essential for PINK1 Import into Mitochondria},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0058435},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131061},
  pages     = {e58435},
  year      = {2013},
  abstract  = {PTEN induced kinase 1 (PINK1) is a serine/threonine kinase in the outer membrane of mitochondria (OMM), and known as a responsible gene of Parkinson's disease (PD). The precursor of PINK1 is synthesized in the cytosol and then imported into the mitochondria via the translocase of the OMM (TOM) complex. However, a large part of PINK1 import mechanism remains unclear. In this study, we examined using cell-free system the mechanism by which PINK1 is targeted to and assembled into mitochondria. Surprisingly, the main component of the import channel, Tom40 was not necessary for PINK1 import. Furthermore, we revealed that the import receptor Tom70 is essential for PINK1 import. In addition, we observed that although PINK1 has predicted mitochondrial targeting signal, it was not processed by the mitochondrial processing peptidase. Thus, our results suggest that PINK1 is imported into mitochondria by a unique pathway that is independent of the TOM core complex but crucially depends on the import receptor Tom70.},
  language  = {en}
}