Abstract：
:Loss-of-function mutations in the genes encoding PINK1 and Parkin (also known as PARK2) are the most common causes of recessive Parkinson's disease. Both together mediate the selective degradation of mitochondrial proteins and whole organelles via the proteasome and the autophagy-lysosome pathway (mitophagy). The mitochondrial kinase PINK1 activates and recruits the E3 ubiquitin ligase Parkin to de-energized mitochondria. However, the cognate E2 co-enzymes of Parkin in this ubiquitin-dependent pathway have not been investigated. Here, we discovered a total of four E2s that either positively or negatively regulate the activation, translocation and enzymatic functions of Parkin during mitochondrial quality control. UBE2D family members and UBE2L3 redundantly charged the RING-HECT hybrid ligase Parkin with ubiquitin, resulting in its initial activation and translocation to mitochondria. UBE2N, however, primarily operated through a different mechanism in order to mediate the proper clustering of mitochondria, a prerequisite for degradation. Strikingly, in contrast to UBE2D, UBE2L3 and UBE2N, depletion of UBE2R1 resulted in enhanced Parkin translocation and clustering upon mitochondrial uncoupling. Our study uncovered redundant, cooperative or antagonistic functions of distinct E2 enzymes in the regulation of Parkin and mitophagy that might suggest a putative role in Parkinson's disease pathogenesis.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Fiesel FC,Moussaud-Lamodière EL,Ando M,Springer Wdoi
10.1242/jcs.147520subject
Has Abstractpub_date
2014-08-15 00:00:00pages
3488-504issue
Pt 16eissn
0021-9533issn
1477-9137pii
jcs.147520journal_volume
127pub_type
杂志文章abstract：:The glucocorticoid receptor and the mineralocorticoid receptor are hormone-dependent transcription factors. They regulate the excitability of rat hippocampus CA1 neurons in a coordinated fashion. We studied the spatial distribution of these transcription factors in nuclei of CA1 neurons by dual labeling immunocytochem...
journal_title：Journal of cell science
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journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：
更新日期：2000-01-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：2002-01-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：1993-11-01 00:00:00
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doi：
更新日期：2002-05-15 00:00:00
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