Function and characteristics of PINK1 in mitochondria.

Function and characteristics of PINK1 in mitochondria.
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DOI:
10.1155/2013/601587
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发表时间:
2013
影响因子:
--
通讯作者:
Kobayashi M
Kobayashi M
中科院分区:
生物学2区
文献类型:
--
作者:
Matsuda S;Kitagishi Y;Kobayashi M

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磷酸酶和张力蛋白同源物诱导的激酶1(PINK1)的突变导致复发性遗传性帕金森病,这是一种与线粒体功能障碍相关的神经退行性疾病。研究支持PINK1的神经保护作用的概念,因为它保护细胞免受损伤介导的线粒体功能障碍,氧化应激和细胞凋亡。PARL是一种线粒体常驻菱形丝氨酸蛋白酶,据报道它介导PINK1的切割。有趣的是,受损的线粒体自噬,一种重要的自噬质量控制机制,清除受损的线粒体细胞,也可能是帕金森病患者PARL突变的疾病发病机制的潜在机制。功能研究表明,PINK1将Parkin招募到线粒体中以启动线粒体自噬。PINK 1是翻译后加工的,其水平在线粒体的健康稳定状态下受到明确调节。因此,PINK1在线粒体健康稳态中起着关键作用。
Mutations in phosphatase and tensin homologue-induced kinase 1 (PINK1) cause recessively inherited Parkinson's disease, a neurodegenerative disorder linked to mitochondrial dysfunction. Studies support the notion of neuroprotective roles for the PINK1, as it protects cells from damage-mediated mitochondrial dysfunction, oxidative stress, and cell apoptosis. PARL is a mitochondrial resident rhomboid serine protease, and it has been reported to mediate the cleavage of the PINK1. Interestingly, impaired mitophagy, an important autophagic quality control mechanism that clears the cells of damaged mitochondria, may also be an underlying mechanism of disease pathogenesis in patients for Parkinson's disease with the PARL mutations. Functional studies have revealed that PINK1 recruits Parkin to mitochondria to initiate the mitophagy. PINK1 is posttranslationally processed, whose level is definitely regulated in healthy steady state of mitochondria. As a consequence, PINK1 plays a pivotal role in mitochondrial healthy homeostasis.
DOI: 10.1083/jcb.201008084
发表时间: 2010-11-29
期刊: The Journal of cell biology
影响因子: --
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