Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Neurobiol Aging. 2013 Nov;34(11):2694.e19-20. doi: 10.1016/j.neurobiolaging.2013.05.021. Epub 2013 Jul 5.
Dysfunctional mitochondria and the mitochondrial chaperone mortalin (HSPA9, GRP75) have been implicated in the pathogenesis of Parkinson disease (PD). We screened 139 early-onset PD (EOPD) patients for mutations in mortalin revealing one missense change (p.L358P) that was absent in 279 control individuals. We also found one additional missense variant among the controls (p.T333K). Although both missense changes were predicted to be disease causing, we detected no differences in subcellular localization, mitochondrial morphology, or respiratory function between wild-type and mutant mortalin. These findings suggest that variants in mortalin (1) are not a major cause of EOPD; (2) occur in patients and controls; and (3) do not lead to functional impairment of mitochondria.
功能失调的线粒体和线粒体伴侣分子 mortalin（HSPA9，GRP75）与帕金森病（PD）的发病机制有关。我们对 139 名早发性帕金森病（EOPD）患者进行了 mortalin 基因突变筛查，发现了一个错义突变（p.L358P），在 279 名对照个体中不存在。我们还在对照组中发现了另一个错义变异体（p.T333K）。尽管这两种错义变化都被预测为致病原因，但我们没有发现野生型和突变型 mortalin 之间在亚细胞定位、线粒体形态或呼吸功能上存在差异。这些发现表明，mortalin 中的变体（1）不是 EOPD 的主要原因；（2）存在于患者和对照组中；（3）不会导致线粒体功能障碍。
