Abstract:
:Genetic analysis of Parkinson disease (PD) has identified several genes whose mutation causes inherited parkinsonism, as well as risk loci for sporadic PD. PTEN-induced kinase 1 (PINK1) and parkin, linked to autosomal recessive PD, act in a common genetic pathway regulating the autophagic degradation of mitochondria, termed mitophagy. We undertook a genome-wide RNAi screen as an unbiased approach to identify genes regulating the PINK1/Parkin pathway. We identified several genes that have a conserved function in promoting mitochondrial translocation of Parkin and subsequent mitophagy, most notably sterol regulatory element binding transcription factor 1 (SREBF1), F-box and WD40 domain protein 7 (FBXW7), and other components of the lipogenesis pathway. The relevance of mechanisms of autosomal recessive parkinsonism to sporadic PD has long been debated. However, with the recent identification of SREBF1 as a risk locus for sporadic PD, our findings suggest a common mechanistic link between autosomal recessive and sporadic PD, and underscore the importance of mitochondrial homeostasis.
journal_name
Proc Natl Acad Sci U S Aauthors
Ivatt RM,Sanchez-Martinez A,Godena VK,Brown S,Ziviani E,Whitworth AJdoi
10.1073/pnas.1321207111subject
Has Abstractpub_date
2014-06-10 00:00:00pages
8494-9issue
23eissn
0027-8424issn
1091-6490pii
1321207111journal_volume
111pub_type
杂志文章abstract::The magnetic microstructure of a natural, finely exsolved intergrowth of submicron magnetite blocks in an ulvöspinel matrix is characterized by using off-axis electron holography in the transmission electron microscope. Single-domain and vortex states in individual blocks, as well as magnetostatic interaction fields b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.262514499
更新日期:2002-12-24 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.7.2729
更新日期:1993-04-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2013-04-16 00:00:00
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更新日期:1990-04-01 00:00:00
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更新日期:1998-12-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1991-08-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
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更新日期:2009-08-04 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2009-12-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1974-06-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2016-02-16 00:00:00