Abstract:
:Maintenance of an intact mitochondrial genome is essential for oxidative phosphorylation in all eukaryotes. Depletion of mitochondrial genome copy number can have severe pathological consequences due to loss of respiratory capacity. In Saccharomyces cerevisiae, several bifunctional metabolic enzymes have been shown to be required for mitochondrial DNA (mtDNA) maintenance. For example, Ilv5 is required for branched chain amino acid biosynthesis and mtDNA stability. We have identified OXA1 and TIM17 as novel multicopy suppressors of mtDNA instability in ilv5 cells. In addition, overexpression of TIM17, but not OXA1, prevents the complete loss of mtDNA in cells lacking the TFAM homologue Abf2. Introduction of the disease-associated A3243G mutant mtDNA into human NT2 teratocarcinoma cells frequently causes mtDNA loss. Yet when human TIM17A is overexpressed in NT2 cybrids carrying A3243G mtDNA, the proportion of cybrid clones maintaining mtDNA increases significantly. TIM17A overexpression results in long-term mtDNA stabilization, since NT2 cybrids overexpressing TIM17A maintain mtDNA at levels similar to controls for several months. Tim17 is a conserved suppressor of mtDNA instability and is the first factor to be identified that can prevent mtDNA loss in a human cellular model of mitochondrial disease.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Iacovino M,Granycome C,Sembongi H,Bokori-Brown M,Butow RA,Holt IJ,Bateman JMdoi
10.1093/hmg/ddn313subject
Has Abstractpub_date
2009-01-01 00:00:00pages
65-74issue
1eissn
0964-6906issn
1460-2083pii
ddn313journal_volume
18pub_type
杂志文章abstract::Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association stu...
journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2014-09-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2011-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:1993-10-01 00:00:00
abstract::Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis ...
journal_title:Human molecular genetics
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更新日期:2012-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/hmg/ddaa276
更新日期:2020-12-23 00:00:00
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更新日期:2014-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/hmg/2.5.525
更新日期:1993-05-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn419
更新日期:2009-03-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg145
更新日期:2003-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/1.2.71
更新日期:1992-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-05-01 00:00:00
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journal_title:Human molecular genetics
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更新日期:2019-10-01 00:00:00
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章,多中心研究
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更新日期:2009-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2013-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2017-08-01 00:00:00
abstract::Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization r...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2011-03-15 00:00:00
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journal_title:Human molecular genetics
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更新日期:2017-04-01 00:00:00