This work package aims at the understanding of key molecular and biochemical mechanisms responsible for mitochondrial disease as a prerequisite for the identification of new drug targets and the development of novel treatments. Patients with clinical features characteristic for mitochondrial diseases recruited by the national networks and entered into the national
/global registry (WP1) and mutations in genes so far not known to be associated with mitochondrial energy metabolism will be identified in WP2. Existing cellular models (available through the biomaterial bank, WP1) will be used to evaluate the functional significance of rare gene variants. This work package will develop new assays needed to determine the function of novel disease associated genes and make optimal use of the wide spectrum of established assays available to the consortium members and has the objectives:
i) to evaluate the causative nature of gene variants identified in novel disease genes,
ii) to develop assays to test functional significance of novel rare gene variants,
iii) to delineate novel pathways involved in the pathogenesis of mitochondrial disorders.