Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
FEBS Lett. 2010 Mar 19;584(6):1073-9. doi: 10.1016/j.febslet.2010.02.016. Epub 2010 Feb 12.
Mutations in PTEN-induced putative kinase 1 (PINK1) cause recessive form of Parkinson's disease (PD). PINK1 acts upstream of parkin, regulating mitochondrial integrity and functions. Here, we show that PINK1 in combination with parkin results in the perinuclear mitochondrial aggregation followed by their elimination. This elimination is reduced in cells expressing PINK1 mutants with wild-type parkin. Although wild-type PINK1 localizes in aggregated mitochondria, PINK1 mutants localization remains diffuse and mitochondrial elimination is not observed. This phenomenon is not observed in autophagy-deficient cells. These results suggest that mitophagy controlled by the PINK1/parkin pathway might be associated with PD pathogenesis.
PTEN 诱导的激酶 1（PINK1）突变导致帕金森病（PD）的隐性形式。PINK1 作用于 parkin 的上游，调节线粒体的完整性和功能。在这里，我们表明 PINK1 与 parkin 结合导致核周线粒体聚集，随后被消除。在表达具有野生型 parkin 的 PINK1 突变体的细胞中，这种消除减少。尽管野生型 PINK1 定位于聚集的线粒体中，但 PINK1 突变体的定位仍然弥散，并且不会观察到线粒体消除。在自噬缺陷细胞中不会观察到这种现象。这些结果表明，由 PINK1/parkin 途径控制的线粒体自噬可能与 PD 的发病机制有关。
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