Kim Yongsung, Park Jeehye, Kim Sunhong, Song Saera, Kwon Seok-Kyu, Lee Sang-Hee, Kitada Tohru, Kim Jin-Man, Chung Jongkyeong
National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-Dong, Yusong-Gu, Taejon 305-701, Republic of Korea.
Biochem Biophys Res Commun. 2008 Dec 19;377(3):975-80. doi: 10.1016/j.bbrc.2008.10.104. Epub 2008 Oct 26.
PTEN-induced putative kinase 1 (PINK1) and Parkin, encoded by their respective genes associated with Parkinson's disease (PD), are linked in a common pathway involved in the protection of mitochondrial integrity and function. However, the mechanism of their interaction at the biochemical level has not been investigated yet. Using both mammalian and Drosophila systems, we here demonstrate that the PINK1 kinase activity is required for its function in mitochondria. PINK1 regulates the localization of Parkin to the mitochondria in its kinase activity-dependent manner. In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. These results demonstrate the biochemical relationship between PINK1, Parkin, and the mitochondria and thereby suggest the possible mechanism of PINK-Parkin-associated PD pathogenesis.
由与帕金森病（PD）相关的各自基因编码的PTEN诱导的假定激酶1（PINK1）和Parkin，在参与保护线粒体完整性和功能的共同途径中相互关联。然而，它们在生化水平上的相互作用机制尚未得到研究。利用哺乳动物和果蝇系统，我们在此证明PINK1激酶活性是其在线粒体中发挥功能所必需的。PINK1以其激酶活性依赖的方式调节Parkin在线粒体中的定位。具体而言，PINK1对Parkin连接区的磷酸化促进其向线粒体的转运，并且Parkin的RING1结构域对此过程至关重要。这些结果证明了PINK1、Parkin和线粒体之间的生化关系，从而提示了与PINK-Parkin相关的PD发病机制的可能机制。
