In humans, both aging diseases such as cardiac dysfunction are associated with the formation of large deletion mutations in the mitochondrial genome (mtDNA). Despite the prominent role of large mtDNA deletions in human aging and disease, the exact molecular mechanism of mtDNA deletion formation remains unknown. I propose to use the model nematode, Caenorhabditis elegans, as a system to genetically screen for genes that are associated with the formation or accumulation of large mtDNA deletion mutations. The identification of the gene(s) responsible for preventing the formation or accumulation of mtDNA deletions would open up fundamentally new scientific avenues for dissecting the genetic pathways associated with mtDNA deletion formation. Genes identified by this study can be considered as new gene targets for human disease for both diagnosis and treatment.
Mitochondria are the """"""""powerhouses"""""""" that create energy in cells. Damage to the mitochondria is associated with both aging and disease in humans. This goal of this research is to use the well-characterized model animal Caenorhabdidits elegans to identify the gene(s) involved in the formation of mitochondrial DNA damage in human disease.