The Ubiquitination of PINK1 Is Restricted to Its Mature 52-kDa Form.
The Ubiquitination of PINK1 Is Restricted to Its Mature 52-kDa Form.
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DOI：
10.1016/j.celrep.2017.06.022
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发表时间：
2017-07-05
期刊：
影响因子：
8.8
通讯作者：
Przedborski S
中科院分区：
文献类型：
--
作者：
Liu Y;Guardia-Laguarta C;Yin J;Erdjument-Bromage H;Martin B;James M;Jiang X;Przedborski S
Along with Parkin, PINK1 plays a critical role in maintaining mitochondrial quality control. Although PINK1 is expressed constitutively, its level is kept low in healthy mitochondria by polyubiquitination and ensuing proteasomal degradation of its mature, 52 kDa, form. We show here that the target of PINK1 polyubiquitination is the mature form and is mediated by ubiquitination of a conserved lysine at position 137. Notably, the full-length protein also contains Lys-137 but is not ubiquitinated. On the basis of our data, we propose that cleavage of full-length PINK1 at Phe-104 disrupts the major hydrophobic membrane-spanning domain in the protein, inducing a conformation change in the resultant mature form that exposes Lys-137 to the cytosol for subsequent modification by the ubiquitination machinery. Thus, the balance between the full-length and mature PINK1 allows its levels to be regulated via ubiquitination of the mature form and ensures that PINK1 functions as a mitochondrial quality control factor. PINK1 mutations cause Parkinson’s disease. PINK1 is cleaved into a shorter 52-kDa form at the mitochondrial membrane, but regulation of the turnover of cleaved PINK1 is unknown. Liu et al. show that polyubiquitination of cleaved PINK1 regulates its degradation via the proteasome.
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DOI：
10.1083/jcb.201008084
发表时间：
2010-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jin SM;Lazarou M;Wang C;Kane LA;Narendra DP;Youle RJ
通讯作者：
Youle RJ
DOI：
10.1073/pnas.96.8.4604
发表时间：
1999-04-13
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
16.6
作者：
Kravtsova-Ivantsiv, Yelena;Sommer, Thomas;Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
影响因子：
4.8
作者：
Becker, Dorothea;Richter, Judith;Voos, Wolfgang
通讯作者：
Voos, Wolfgang
影响因子：
13.3
作者：
Gelmetti, Vania;De Rosa, Priscilla;Valente, Enza Maria
通讯作者：
Valente, Enza Maria