Functional characterization of mitochondrial DNA maintenance proteins

We applied computational approaches and integrative systems biology methods to identify novel proteins involved in mtDNA maintenance.The aim of this project is functional characterization of the candidate proteins identified by computational approaches. Candidate proteins will be knocked down in cell lines followed by functional measurements of mitochondrial functioning like, mtDNA quality and quantity, mitochondrial transcripts, OXPHOS integrity, subcellular localization studies and others.

The discovery and functional characterization of novel components of mtDNA maintenance will improve our understanding of these processes in health and disease. Moreover, it will improve genetic diagnostic tests and open possibilities for designing therapeutic interventions, improving quality of life for patients with mitochondrial disorders.

Mitochondrial disorders are the most common inherited metabolic disorders affecting over 1 in 5000 people. Although rapid progress in characterizing the mitochondrial proteome has fueled progress in understanding the role of mitochondria in health and disease, functional information is lacking for half of the proteins in the mitochondrial proteome. Moreover, the mitochondrial proteome is believed to be far from complete. As a result, 40-50% of mitochondrial patients remain genetically undiagnosed.