MitMed: identification and characterization of new disease genes for mitochondrial disorders

Mitochondria are the powerhouses of the cell and produce most of the ATP, the energetic currency of the cell. Mitochondrial dysfunction is associated with an energy deficit in the organs and tissues with the highest energetic demand, such as brain, heart and skeletal muscle, leading to mitochondrial disease. Mitochondria are under the double genetic control of their own DNA and of nuclear DNA, which encodes for the vast majority of the mitochondrial proteins. Accordingly, mutations in either the nuclear or mitochondrial DNA can lead to mitochondrial dysfunction and disease. Given the extreme clinical, biochemical, and genetic complexity of these conditions, reaching a certain diagnosis is often challenging, and still now about 50% of the cases remains undiagnosed. However, next generation sequencing techniques offer now the opportunity to expand our diagnostic output even on single patients. MitMed thus aims at significantly contributing to compile the list of disease genes for mitochondrial disorders.
A second challenge in the mitochondrial disease field is that most of the recently identified disease genes encode proteins of unknown function. MitMed will exploit mass spectrometry-based techniques to identify the interactors of newly or recently identified disease genes, and thus clarify the pathways in which they are involved.
Finally, the third challenge is to understand the pathogenetic mechanisms of mitochondrial diseases, an essential step to identify new therapeutic options. MitMed will exploit mouse, fly and yeast models to dissect the molecular pathogenesis of the most interesting disease genes identified during its lifetime.