Cytoplasmic localization and proteasomal degradation of N-terminally cleaved form of PINK1

被引:88
作者
Takatori, Sho [1 ]
Ito, Genta [1 ]
Iwatsubo, Takeshi [1 ]
机构
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Bunkyo Ku, Tokyo 1130033, Japan
关键词
Parkinson's disease; PINK1; mitochondria; proteasome;
D O I
10.1016/j.neulet.2007.10.019
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mutations in PTEN-induced putative kinase 1 (PINK1) gene have been linked to an autosomal recessive form of familial Parkinson's disease. PINK1 encodes a predicted mitochondrial protein kinase. Although the mitochondrial localization of PINK1 has been suggested, the exact subcellular compartment in which PINK1 exerts its cytoprotective function is elusive. Thus, we studied the subcellular distribution and metabolism of PINK1 in cultured cells. Immunocytochemical analysis showed that PINK1 resides in cytoplasm in addition to mitochondria, and that the mitochondrial localization is dependent on its N-terminal sequence. Cellular expression of PINK1 yielded several N-terminally cleaved fragments as well as the full-length protein, among which the 54 kDa fragment (Delta N 54 kDa) was highly accumulated in the presence of proteasome inhibitors. Endogenous PINK1 was detected dominantly in the form of Delta N 54 kDa upon proteasome inhibition. Rapid turnover of Delta N 54 kDa further supported its higher susceptibility to proteasomal degradation compared with that of full-length protein. These results indicate that Delta N 54 kDa PINK1 undergoes constitutive degradation by proteasome, and underscore the significance of its localization in cytoplasm, especially in the N-terminally processed form. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:13 / 17
页数:5
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