Objectif The final goal of the project is to better understand the mechanisms involved in mitochondrial disorders in children caused by the isolated or combined respiratory chain complex I deficiency. Mitochondrial disorders are the most frequent cause of inborn metabolic errors, affecting 1 individual in 5000. Symptoms begin at birth or in early childhood in most cases and generally present as multi-system disorders with a fatal outcome. The majority of the patients die within a few years of the first clinical manifestation. Currently, the genetic origin of the isolated or combined complex I deficiency can be resolved only in the minority of cases suggesting that mutations in yet-unknown factors are a very important cause of disease. At present, the biogenesis of the mitochondrial respiratory chain enzymes is far from understood. Recently, functional complementation and bioinformatic studies carried out in the laboratory of prof. Shoubridge (McGill University, the outgoing host) have led to the identification of two complex I assembly factors and a translational activator for a subunit of complex IV. In this study, in collaboration with prof. Shoubridge, new information on the pathogenesis of mitochondrial disorders is obtained by monitoring the cellular responses at the functional, translational and protein level in different conditions and species. Novel pathogenic mutations will be identified as the underlying genetic cause of the isolated or combined complex I defect in Finnish pediatric patients. In addition, systematic screening of respiratory chain deficient mutants and studies on mice and plants will lead to the discovery of novel factors that control the biogenesis of the mitochondrial respiratory chain. This study will be of significant impact on the medical field by providing new targets for genetic analysis of patients with respiratory chain deficiency. The results of this study can be utilized in the genetic counselling of the patients and their family. Champ scientifique natural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2010-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development" Appel à propositions FP7-PEOPLE-2010-IOF Voir d’autres projets de cet appel Régime de financement MC-IOF - International Outgoing Fellowships (IOF) Coordinateur OULUN YLIOPISTO Contribution de l’UE € 157 532,00 Adresse PENTTI KAITERAN KATU 1 90014 Oulu Finlande Voir sur la carte Région Manner-Suomi Pohjois- ja Itä-Suomi Pohjois-Pohjanmaa Type d’activité Higher or Secondary Education Establishments Contact administratif Kari Majamaa (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
