The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity
作者: Maya AndoFabienne C. FieselRoman HudecThomas R. CaulfieldKotaro OgakiPaulina Górka-SkoczylasDariusz KoziorowskiAndrzej FriedmanLi ChenValina L. DawsonTed M. DawsonGuojun BuOwen A. RossZbigniew K. WszolekWolfdieter Springer
作者单位: 1Mayo Clinic
2Mayo Clinic Graduate School of Biomedical Sciences
3Institute of Mother and Child
4Warsaw University
5Medical University of Warsaw
6Johns Hopkins University School of Medicine
7Adrienne Helis Malvin Medical Research Foundation
8Mayo Clinic;
刊名: Molecular Neurodegeneration, 2017, Vol.12 (1)
来源数据库: Springer Journal
DOI: 10.1186/s13024-017-0174-z
关键词: Parkinson’s diseasePINK1PARKINUbiquitinMitophagyAutophagyPARK2MitochondriaPhospho-ubiquitinE3 ubiquitin ligase
英文摘要: Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson’s disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degradation in order to prevent their accumulation and eventually cell death. Homozygous or compound heterozygous loss of either gene function disrupts this protective pathway, though at different steps and by distinct mechanisms. While structure and function of PARKIN variants have been well studied, PINK1 mutations remain poorly characterized, in particular under endogenous conditions. A better understanding of the exact molecular pathogenic mechanisms...
原始语种摘要: Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson’s disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degradation in order to prevent their accumulation and eventually cell death. Homozygous or compound heterozygous loss of either gene function disrupts this protective pathway, though at different steps and by distinct mechanisms. While structure and function of PARKIN variants have been well studied, PINK1 mutations remain poorly characterized, in particular under endogenous conditions. A better understanding of the exact molecular pathogenic mechanisms...
全文获取路径: Springer  (合作)
分享到:
来源刊物:
影响因子:4.007 (2012)

×
关键词翻译
关键词翻译
  • ubiquitin 泛激素
  • kinase 激酶
  • ligase 连接酶
  • protein 蛋白质
  • mitochondria 线粒体
  • endogenous 内成的
  • mutation 变种
  • crucial 有决定性的
  • heterozygous 杂合的
  • underlying 下伏的