Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism
Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism
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DOI：
10.1093/hmg/ddi377
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发表时间：
2005-11-15
影响因子：
3.5
通讯作者：
Casari, G
中科院分区：
文献类型：
--
作者：
Silvestri, L;Caputo, V;Casari, G
帕金森病（PD）是一种进行性神经退行性疾病，与大脑黑质纹状体通路中多巴胺能神经元的选择性缺失有关。尽管家族性帕金森病形式总体较为罕见，但与该疾病相关的单个基因的鉴定为神经退行性变的可能机制提供了重要见解。最近，一种假定的线粒体激酶PINK1在一种遗传性帕金森综合征中被发现存在突变。在此，我们描述了PINK1突变赋予不同的自磷酸化活性，该活性受蛋白质的C末端部分调节。我们还明确地证明了野生型和突变型PINK1蛋白的线粒体定位，并证明PINK1的一个短的N末端部分足以使其靶向线粒体。
Parkinson's disease (PD) is a progressive neurodegenerative illness associated with a selective loss of dopaminergic neurons in the nigrostriatal pathway of the brain. Despite the overall rarity of the familial forms of PD, the identification of single genes linked to the disease has yielded crucial insights into possible mechanisms of neurodegeneration. Recently, a putative mitochondrial kinase, PINK1, has been found mutated in an inherited form of parkinsonism. Here, we describe that PINK1 mutations confer different autophosphorylation activity, which is regulated by the C-terminal portion of the protein. We also demonstrate the mitochondrial localization of both wild-type and mutant PINK1 proteins unequivocally and prove that a short N-terminal part of PINK1 is sufficient for its mitochondrial targeting.