UNIVERSITY OF CALIFORNIA LOS ANGELES
Mitochondrial DNA Quality Control and Neurodegeneration
Parkinson's disease & PD-related disorders
Mitochondrial DNA, Quality Control, Nerve Degeneration, mitochondrial DNA mutation, PINK1 gene
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.
PUBLIC HEALTH RELEVANCE: The central focus of this proposal explores how to fill a knowledge gap – to identify molecular mechanisms of mitochondrial DNA quality control and age-dependent neurodegeneration. The identification of these mechanisms will allow us to develop effective drug targets for delaying aging and age-dependent cellular dysfunction in neurons. This will improve our understanding of Parkinson’s disease, and may provide important insight into aging and other neurodegenerative disorders including Alzheimer’s disease.