A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30
Yue, Wen1,2; Chen, Ziheng1,2; Liu, Haiyang3; Yan, Chen3; Chen, Ming1,2; Feng, Du4; Yan, Chaojun; Wu, Hao1,2; Du, Lei1,2; Wang, Yueying1,2; Liu, Jinhua4; Huang, Xiaohu5; Xia, Laixin1; Liu, Lei1; Wang, Xiaohui1; Jin, Haijing1; Wang, Jun1; Song, Zhiyin6; Hao, Xiaojiang3; Chen, Quan1,2,4
Corresponding AuthorChen, Q (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Lab Apoptosis & Mitochondrial Biol, Beijing 100101, Peoples R China. ; haoxj@mail.kib.ac.cn ; chenq@ioz.ac.cn
2014-04-01
Source PublicationCELL RESEARCH
ISSN1001-0602
Volume24Issue:4Pages:482-496
Abstract

Mitochondrial fusion is a highly coordinated process that mixes and unifies the mitochondrial compartment for normal mitochondrial functions and mitochondrial DNA inheritance. Dysregulated mitochondrial fusion causes mitochondrial fragmentation, abnormal mitochondrial physiology and inheritance, and has been causally linked with a number of neuronal diseases. Here, we identified a diterpenoid derivative 15-oxospiramilactone (S3) that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfn1 or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of S3. The inhibition of USP30 by S3 leads to an increase of non-degradative ubiquitination of Mfn1/2, which enhances Mfn1 and Mfn2 activity and promotes mitochondrial fusion. Thus, through the use of an inhibitor of USP30, our study uncovers an unconventional function of non-degradative ubiquitination of Mfns in promoting mitochondrial fusion.

KeywordMitochondrial Fusion Mitofusin1/2 Deubiquitinase Usp30 15-oxospiramilactone
Subject AreaCell Biology
DOI10.1038/cr.2014.20
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000334400600010
Citation statistics
Cited Times:70[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/18040
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Lab Apoptosis & Mitochondrial Biol, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochemistry & Plant Resources W, Kunming 650204, Yunnan, Peoples R China
4.Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China
5.Peking Univ, Peking Tsinghua Ctr Life Sci, Inst Mol Med, Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China
6.Wuhan Univ, Coll Life Sci, Wuhan 430072, Hunan, Peoples R China
Recommended Citation
GB/T 7714
Yue, Wen,Chen, Ziheng,Liu, Haiyang,et al. A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30[J]. CELL RESEARCH,2014,24(4):482-496.
APA Yue, Wen.,Chen, Ziheng.,Liu, Haiyang.,Yan, Chen.,Chen, Ming.,...&Chen, Quan.(2014).A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30.CELL RESEARCH,24(4),482-496.
MLA Yue, Wen,et al."A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30".CELL RESEARCH 24.4(2014):482-496.
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