Phosphorylated ubiquitin chain is the genuine Parkin receptor.
Phosphorylated ubiquitin chain is the genuine Parkin receptor.
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磷酸化的泛素链是真正的parkin受体。
DOI：
10.1083/jcb.201410050
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发表时间：
2015-04-13
期刊：
影响因子：
--
通讯作者：
Matsuda N
中科院分区：
文献类型：
--
作者：
Okatsu K;Koyano F;Kimura M;Kosako H;Saeki Y;Tanaka K;Matsuda N
pink1磷酸化的泛素链是真正的Parkin受体，招募Parkin去极化线粒体。PINK1选择性地招募Parkin去极化线粒体，通过泛素化隔离和去除受损的线粒体。这一过程的功能障碍易导致家族隐性帕金森病的发展。尽管已经提出了各种关于募集过程的模型，但没有一个能充分解释积累的数据，因此Parkin中PINK1募集的分子基础仍有待充分阐明。在这项研究中，我们发现在缺乏PINK1的情况下，拟磷四泛素（S65D）的线性泛素链将Parkin招募到激活的线粒体，而野生型四泛素链则不会。在更生理相关的条件下，溶酶体磷酸化的多泛素链将拟磷帕金招募到溶酶体中。细胞泛素替代系统证实，泛素磷酸化确实是帕金易位的必要条件。此外，通过细胞免疫沉淀和重组蛋白体外重构，检测了拟磷Parkin与磷酸化多泛素链之间的物理相互作用。因此，我们提出磷酸化的泛素链作为真正的Parkin受体募集到去极化线粒体。
PINK1-phosphorylated ubiquitin chain is the genuine Parkin receptor that recruits Parkin to depolarized mitochondria. PINK1 selectively recruits Parkin to depolarized mitochondria for quarantine and removal of damaged mitochondria via ubiquitylation. Dysfunction of this process predisposes development of familial recessive Parkinson’s disease. Although various models for the recruitment process have been proposed, none of them adequately explain the accumulated data, and thus the molecular basis for PINK1 recruitment of Parkin remains to be fully elucidated. In this study, we show that a linear ubiquitin chain of phosphomimetic tetra-ubiquitin(S65D) recruits Parkin to energized mitochondria in the absence of PINK1, whereas a wild-type tetra-ubiquitin chain does not. Under more physiologically relevant conditions, a lysosomal phosphorylated polyubiquitin chain recruited phosphomimetic Parkin to the lysosome. A cellular ubiquitin replacement system confirmed that ubiquitin phosphorylation is indeed essential for Parkin translocation. Furthermore, physical interactions between phosphomimetic Parkin and phosphorylated polyubiquitin chain were detected by immunoprecipitation from cells and in vitro reconstitution using recombinant proteins. We thus propose that the phosphorylated ubiquitin chain functions as the genuine Parkin receptor for recruitment to depolarized mitochondria.
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影响因子：
4.5
作者：
Liu S;Sawada T;Lee S;Yu W;Silverio G;Alapatt P;Millan I;Shen A;Saxton W;Kanao T;Takahashi R;Hattori N;Imai Y;Lu B
通讯作者：
Lu B
影响因子：
3.7
作者：
Chew KC;Matsuda N;Saisho K;Lim GG;Chai C;Tan HM;Tanaka K;Lim KL
通讯作者：
Lim KL
DOI：
10.1083/jcb.201210111
发表时间：
2013-01-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lazarou M;Narendra DP;Jin SM;Tekle E;Banerjee S;Youle RJ
通讯作者：
Youle RJ
DOI：
10.1083/jcb.200910140
发表时间：
2010-04-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Matsuda N;Sato S;Shiba K;Okatsu K;Saisho K;Gautier CA;Sou YS;Saiki S;Kawajiri S;Sato F;Kimura M;Komatsu M;Hattori N;Tanaka K
通讯作者：
Tanaka K
Parkin对泛素 - 蛋白酶体系统的广泛激活对于线粒体至关重要。
影响因子：
3.5
作者：
Chan NC;Salazar AM;Pham AH;Sweredoski MJ;Kolawa NJ;Graham RL;Hess S;Chan DC
通讯作者：
Chan DC