PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy

PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy
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DOI:
10.1016/j.febslet.2010.02.016
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发表时间:
2010-03-19
期刊:
影响因子:
3.5
通讯作者:
Hattori, Nobutaka
Hattori, Nobutaka
中科院分区:
生物学3区
文献类型:
--
作者:
Kawajiri, Sumihiro;Saiki, Shinji;Hattori, Nobutaka

文献摘要

被引文献

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PTEN 诱导的推定激酶 1 (PINK1) 突变会导致隐性帕金森病 (PD)。 PINK1 作用于 Parkin 上游,调节线粒体完整性和功能。在这里,我们证明 PINK1 与 Parkin 结合会导致核周线粒体聚集,然后将其消除。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 突变体定位仍然是分散的,并且未观察到线粒体消除。在自噬缺陷的细胞中未观察到这种现象。这些结果表明,PINK1/parkin 通路控制的线粒体自噬可能与 PD 发病机制相关。 结构摘要:MINT-7557195:PINK1 (uniprotkb: Q9BXM7) 通过抗标签共免疫沉淀与 LC3 (uniprotkb: Q9GZQ8) 发生物理相互作用 (MI: 0915) (MI: 0007)MINT-7557109: LC3 (uniprotkb: Q9GZQ8) 和 PINK1 (uniprotkb: Q9BXM7) 通过荧光显微镜共定位 (MI: 0403) (MI: 0416)MINT-7557121: tom20 (uniprotkb: Q15388) 和 PINK1 (uniprotkb: Q9BXM7)通过荧光显微镜共定位(MI:0403)(MI:0416)MINT-7557138:parkin(uniprotkb:O60260),PINK1(uniprotkb:Q9BXM7)和tom20(uniprotkb:Q15388)通过荧光显微镜共定位(MI:0403)(MI: 0416)MINT-7557173:LC3 (uniprotkb: Q9GZQ8) 通过抗诱饵共免疫沉淀 (MI: 0006)(C) 与 PINK1 (uniprotkb: Q9BXM7) 物理相互作用 (MI: 0915) (C) 2010 年欧洲生化学会联合会。由 Elsevier B.V 出版。保留所有权利。
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.Structured summary:MINT-7557195: PINK1 (uniprotkb: Q9BXM7) physically interacts (MI: 0915) with LC3 ( uniprotkb: Q9GZQ8) by anti tag coimmunoprecipitation ( MI: 0007)MINT-7557109: LC3 ( uniprotkb: Q9GZQ8) and PINK1 ( uniprotkb: Q9BXM7) colocalize ( MI: 0403) by fluorescence microscopy ( MI: 0416)MINT-7557121: tom20 ( uniprotkb: Q15388) and PINK1 ( uniprotkb: Q9BXM7) colocalize ( MI: 0403) by fluorescence microscopy ( MI: 0416)MINT-7557138: parkin ( uniprotkb: O60260), PINK1 ( uniprotkb: Q9BXM7) and tom20 ( uniprotkb: Q15388) colocalize ( MI: 0403) by fluorescence microscopy ( MI: 0416)MINT-7557173: LC3 ( uniprotkb: Q9GZQ8) physically interacts ( MI: 0915) with PINK1 ( uniprotkb: Q9BXM7) by anti bait coimmunoprecipitation ( MI: 0006)(C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.