Beyond Deubiquitylation: USP30-Mediated Regulation of Mitochondrial Homeostasis

  • Jiayun Hou
  • Mohmmad Eldeeb
  • Xiangdong WangEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1038)


Mutations or sequence aberrations in the Parkin gene are among the most common causes of autosomal recessive Parkinson’s disorder (PD). Parkin, a cytoplasmic E3 ubiquitin ligase, is involved in mitochondrial quality control pathways, including mitochondrial fission and mitophagy by autophagy-related genes. Parkin mediates the covalent addition of ubiquitin (Ub) chains to Lys 6, Lys 11, and Lys 63 on diverse mitochondrial-related target proteins. USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2. USP30 preferentially mediates the removal of Ub chains from Lys 6 and Lys 11 on mitochondria-derived proteins. USP30 mediates the removal of the ubiquitin chains added by Parkin. It was demonstrated that overexpression of USP30 triggers the mitochondrial dynamic signaling toward elevated fusion and reduced fission and halts mitochondrial clearance via mitophagy. Although mounting lines of evidences reveal the pivotal role of Parkin in mitochondrial quality control pathways, the crucial role of deubiquitinases including the USP30 deubiquitinase is emerging. Herein, we review briefly the role of USP30 in the dynamic networks of mitochondrial quality control and its physiological implications.


Mitochondrial fusion Mitochondrial fission Mitophagy Deubiquitylation USP30 



The work was supported by Zhongshan Distinguished Professor Grant (XDW), the National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81300010), the Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600, 14431905100), the operation funding of Shanghai Institute of Clinical Bioinformatics, the Ministry of Education for Academic Special Science and Research Foundation for PhD Education (20130071110043), and the National Key Research and Development Program (2016YFC0902400, 2017YFSF090207).


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Copyright information

© The Editor(s) (if applicable) and The Author(s) 2018 2017

Authors and Affiliations

  1. 1.Zhongshan Hospital Institute of Clinical ScienceFudan UniversityShanghaiChina
  2. 2.Shanghai Institute of Clinical Bioinformatics, Biomedical Research CenterShanghaiChina
  3. 3.Department of BiochemistryUniversity of AlbertaEdmontonCanada
  4. 4.Zhongshan Hospital Institute of Clinical ScienceFudan University, Shanghai Medical CollegeShanghaiChina

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