Recessive parkinsonism and mitochondrial function

我们一直在研究线粒体功能如何影响神经元的存活，特别是在遗传性帕金森病的背景下。为此，我们一直在研究加速老化模型，包括一个线粒体聚合酶γ突变，减少了酶的校对活性，导致线粒体DNA突变的积累。我们以前报道过，使用一系列高含量的技术，PolG突变动物的线粒体复合物I组装的损失。鉴于先前来自细胞培养实验的数据表明DJ-1缺陷与对复合物I抑制剂（如鱼藤酮或MPP+）的敏感性增加有关，因此我们预期PolG和DJ-1动物杂交将导致多巴胺能表型的丧失。然而，尽管在适当的动力研究中进行了广泛的调查，但我们没有发现双突变体中神经元丢失的任何证据。

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.