Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Department of Neurology, Haukeland University Hospital, Bergen, Norway.
PLoS One. 2019 Jul 19;14(7):e0219909. doi: 10.1371/journal.pone.0219909. eCollection 2019.
Several proteins linked to familial Parkinson disease have been associated with mitochondrial (dys-)function and have been described to reside within mitochondria. The putative mitochondrial and sub-mitochondrial localization of these proteins remains disputed, however, potentially due to conflicting results obtained by diverging technical approaches. Using the high-resolution poly-ADP-ribose assisted protein localization assay that also allows for detection of low level and even partial mitochondrial matrix localization, we demonstrate here that DJ-1, but not LRRK2 or α-synuclein, resides in the mitochondrial matrix. The localization of the proteins was not changed in cellular stress models of Parkinson disease and, in case of α-synuclein, not affected by pathological mutations. Our results verify the ability of DJ-1 to carry out its role also from within mitochondria and suggest that LRRK2 and α-synuclein may interact with and affect mitochondria from outside the mitochondrial matrix.
几种与家族性帕金森病相关的蛋白质与线粒体（功能障碍）有关，并被描述为存在于线粒体中。然而，这些蛋白质的假定线粒体和亚线粒体定位仍然存在争议，这可能是由于不同技术方法获得的相互矛盾的结果。本研究使用高分辨率聚 ADP-核糖辅助蛋白定位检测，该方法还可以检测低水平甚至部分线粒体基质定位，我们在此证明 DJ-1 存在于线粒体基质中，但 LRRK2 或 α-突触核蛋白不存在于线粒体基质中。这些蛋白质的定位在帕金森病的细胞应激模型中没有改变，并且在 α-突触核蛋白的情况下，不受病理突变的影响。我们的研究结果验证了 DJ-1 从线粒体内部发挥其作用的能力，并表明 LRRK2 和 α-突触核蛋白可能从线粒体基质外部与线粒体相互作用并影响线粒体。
