Mitochondrial DNA Quality Control and Neurodegeneration

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DESCRIPTION (provided by applicant): Neurodegenerative disorders affect more than 50% of the population over the age of 80, and no treatment can halt the progression of the disease. The strongest risk factor for most, if not all, neurodegenerative disorders are aging. Accumulation of mitochondrial DNA (mtDNA) mutations is seen during human aging and leads to cellular dysfunction and death. Thus strategies that reduce the mtDNA load and improve mitochondrial DNA quality are likely to delay aging and reduce the age-related pathologies of neurodegenerative diseases. We have generated a unique tool in living Drosophila melanogaster that contains engineered mtDNA mutations. We aim to use these flies to carry out genome-wide genetic screens to identify those genes, when mutated, lead to suppression or enhancement of the mitochondrial quality control.