期刊
AUTOPHAGY
卷 11, 期 2, 页码 428-429出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2015.1009794
关键词
deubiquitination; K6 Ub-linkages; mitophagy; PARK2/Parkin; USP8
类别
The Parkinson disease (PD)-associated E3-ubiquitin (Ub) ligase PARK2/parkin plays a central role in many stress response pathways, and in particular, in mitochondrial quality control. Within this pathway, PARK2 activation is accompanied by a robust increase in its autoubiquitination, followed by clearance of the damaged mitochondria by selective autophagy (mitophagy). Yet, little is known about how this auto-ubiquitination is regulated during mitophagy. In our study, we demonstrate that PARK2 forms predominantly K6-linked Ub conjugates on itself. Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in the pathway. When USP8 is silenced, a persistence of K6-linked Ub conjugates on PARK2 delays both its translocation to damaged mitochondria and successful completion of mitophagy. Taken together, these findings implicate a novel role for K6linked Ub conjugates and USP8-mediated deubiquitination in the regulation of PARK2 in mitochondrial quality control.
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