التفاصيل البيبلوغرافية
| العنوان: |
USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria. |
| المؤلفون: |
Cunningham, Christian N., Baughman, Joshua M., Phu, Lilian, Tea, Joy S., Yu, Christine, Coons, Mary, Kirkpatrick, Donald S., Bingol, Baris, Corn, Jacob E. |
| المصدر: |
Nature Cell Biology; Feb2015, Vol. 17 Issue 2, p160-169, 10p, 1 Diagram, 13 Graphs |
| مصطلحات موضوعية: |
UBIQUITIN ligases, MITOCHONDRIA, PARKINSON'S disease, UBIQUITINATION, MASS spectrometry, AUTOPHAGY |
| مستخلص: |
Multiple lines of evidence indicate that mitochondrial dysfunction is central to Parkinson's disease. Here we investigate the mechanism by which parkin, an E3 ubiquitin ligase, and USP30, a mitochondrion-localized deubiquitylase, regulate mitophagy. We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. Using mass spectrometry, we show that recombinant USP30 preferentially removes these linkage types from intact ubiquitylated mitochondria and counteracts parkin-mediated ubiquitin chain formation in cells. These results, combined with a series of chimaera and localization studies, afford insights into the mechanism by which a balance of ubiquitylation and deubiquitylation regulates mitochondrial homeostasis, and suggest a general mechanism for organelle autophagy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
