Recessive parkinsonism and mitochondrial function

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We have been working on how mitochondrial function influences neuronal survival, particularly in the context of inherited forms of parkinsonism. To this end, we have been examining accelerated aging models including one with a mutation in the mitochondrial polymerase gamma that diminishes proofreading activity of the enzyme, leading to accumulation of mitochondrial DNA mutations. We previously reported that, using a series of high content techniques, PolG mutant animals had loss of mitochondrial complex I assembly. Given that previous data from cell culture experiments suggested that DJ-1 deficiency was associated with an increased sensitivity to complex I inhibitors such as rotenone or MPP+, we therefore expected that crossing PolG and DJ-1 animals would result in loss of dopaminergic phenotypes. However, despite extensive investigation in appropriately powered studies we did not find any evidence of neuronal loss in the double mutants.