Development of diagnostic, biochemical and molecular methods, the prevention and the study of treatment of OXPHOS deficiency.

Mitochondrial cytopathies are a heterogeneous group of progressive disorders caused by a dysfunction of the oxidative phosphorylation (OXPHOS) system, a complex pathway linking respiration to ATP synthesis. They present as multisystemic diseases, with a particular vulnerability in most energy demanding tissues. They are now recognized as an important cause of morbidity or mortality in the general population with a broad impact on public health. The OXPHOS consists of five large multi heteromeric enzymes (complexes I to V), embedded in the inner mitochondrial membrane. Mitochondrial genetics is rather complex as both the nuclear and mitochondrial genomes are involved in the efficient functioning of the complexes. Both maternal and Mendelian patterns of inheritance are possible. Of the more than 80 structural components, only 13 subunits are encoded by the mitochondrial DNA (mtDNA). In addition, a large set of proteins, necessary for assembly, protein folding, import of subunits and intergenomic signaling, are making the molecular diagnosis of mitochondrial disorders particularly challenging. The past two decades, numerous pathogenic gene defects causing mitochondrial diseases have already been identified in single patients or families, but a vast majority of patients remain uncharacterized at the molecular level. An inter university collaboration between the Centre for Medical Genetics (VUB) and the Mitochondrial Laboratory Gent (UGent) is important for diagnostics and research in the field of mitochondrial disorders, and acts as a National Reference Centre in Belgium.