Analysis of neuronal phosphoproteome reveals PINK1 regulation of BAD function and cell death
Wan, Huida3; Tang, Bin3; Liao, Xun2; Zeng, Qiufang3; Zhang, Zhuohua1; Liao, Lujian3
刊名CELL DEATH AND DIFFERENTIATION
2018-05-01
卷号25期号:5页码:904-917
ISSN号1350-9047
DOI10.1038/s41418-017-0027-x
产权排序2
文献子类Article
英文摘要PINK1 mutations that disrupt its kinase activity cause autosomal recessive early onset Parkinson's disease (PD). Although research in recent years has elucidated a PINK1-Parkin pathway of mitophagy activation that requires PINK1 kinase activity, mitophagy-independent functions of PINK1 and their possible roles in PD pathogenesis have been proposed. Using an unbiased quantitative mass spectrometry approach to analyze the phosphoproteome in primary neurons from wild type and Pink1 knockout mice after mitochondrial depolarization, we uncovered PINK1-regulated phosphorylation sites, which involve coordinated activation of multiple signaling pathways that control cellular response to stress. We further identified the pro-apoptotic protein BAD as a potential mitochondrial substrate of PINK1 both in vitro and in vivo, and found that cells more susceptible to a12poptosis induced by mitochondrial damage can be rescued by phosphorylation mimic BAD. Our results thus suggest that PINK1 kinase activity is important for pro-apoptotic protein function in regulation of cell death.
学科主题Cell ; Developmental Biology
URL标识查看原文
WOS关键词PARKINSONS-DISEASE ; PHOSPHORYLATION ; SURVIVAL ; KINASE ; MITOPHAGY ; PROTEIN ; DEPOLARIZATION ; DEGRADATION ; TRANSLOCATION ; MITOCHONDRIA
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000431770600008
内容类型期刊论文
源URL[http://210.75.237.14/handle/351003/30259]  
专题国家天然药物工程技术研究中心_天然产物研究
作者单位1.Institute of Precision Medicine, State key laboratory of Medical Genetics, the Xiangya Hospital and the Xiangya Medical School,Central South University, Changsha, Hunan 410078, China
2.Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Sichuan, Peoples R China;
3.Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, and Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University,Shanghai 200241, China;
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GB/T 7714
Wan, Huida,Tang, Bin,Liao, Xun,et al. Analysis of neuronal phosphoproteome reveals PINK1 regulation of BAD function and cell death[J]. CELL DEATH AND DIFFERENTIATION,2018,25(5):904-917.
APA Wan, Huida,Tang, Bin,Liao, Xun,Zeng, Qiufang,Zhang, Zhuohua,&Liao, Lujian.(2018).Analysis of neuronal phosphoproteome reveals PINK1 regulation of BAD function and cell death.CELL DEATH AND DIFFERENTIATION,25(5),904-917.
MLA Wan, Huida,et al."Analysis of neuronal phosphoproteome reveals PINK1 regulation of BAD function and cell death".CELL DEATH AND DIFFERENTIATION 25.5(2018):904-917.
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