The Ubiquitination of PINK1 Is Restricted to Its Mature 52-kDa Form

Cell Reports

Hediye Erdjument-Bromage¹  Michael James²  Jiang Yin²  Brittany Martin³  Serge Przedborski³  Cristina Guardia-Laguarta³  Yuhui Liu³  Xuejun Jiang⁴ 

[1] Department of Biochemistry and Molecular Pharmacology, New York University, New York, NY 10016, USA;Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada;Departments of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA;Program in Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;

关键词: PINK1;    ubiquitination;    mitochondria;    Parkinson’s disease;    mitophagy;    proteasome;   

DOI  :  10.1016/j.celrep.2017.06.022

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown