Phosphorylation of Human TFAM in Mitochondria Impairs DNA Binding and Promotes Degradation by the AAA<sup>+</sup> Lon Protease

doi:10.1016/j.molcel.2012.10.023

科研成果详情

题名	Phosphorylation of Human TFAM in Mitochondria Impairs DNA Binding and Promotes Degradation by the AAA⁺ Lon Protease
作者	Lu, Bin 4; Lee, Jae 3,4; Nie, Xiaobo 4; Li, Min 4; Morozov, Yaroslav I.1; Venkatesh, Sundararajan 4; Bogenhagen, Daniel F.2; Temiakov, Dmitry 1; Suzuki, Carolyn K.4
发表期刊	Molecular Cell 影响因子和分区
语种	英语
原始文献类型	Article
摘要	Human mitochondrial transcription factor A (TFAM) is a high-mobility group (HMG) protein at the nexus of mitochondrial DNA (mtDNA) replication, transcription, and inheritance. Little is known about the mechanisms underlying its posttranslational regulation. Here, we demonstrate that TFAM is phosphorylated within its HMG box 1 (HMG1) by cAMP-dependent protein kinase in mitochondria. HMG1 phosphorylation impairs the ability of TFAM to bind DNA and to activate transcription. We show that only DNA-free TFAM is degraded by the Lon protease, which is inhibited by the anticancer drug bortezomib. In cells with normal mtDNA levels, HMG1-phosphorylated TFAM is degraded by Lon. However, in cells with severe mtDNA deficits, nonphosphorylated TFAM is also degraded, as it is DNA free. Depleting Lon in these cells increases levels of TFAM and upregulates mtDNA content, albeit transiently. Phosphorylation and proteolysis thus provide mechanisms for rapid fine-tuning of TFAM function and abundance in mitochondria, which are crucial for maintaining and expressing mtDNA. © 2013 Elsevier Inc.
资助项目	National Institutes of Health[R01GM061095];
ISSN	1097-2765
卷号	49 期号:1 页码:121-132
DOI	10.1016/j.molcel.2012.10.023
收录类别	SCOPUS
发表日期	2013-01-10
URL	查看原文
Scopus记录号	2-s2.0-84872271398
CNS重要论文	CNS重要论文
自科自定义期刊分类	T2(B)类
引用统计	被引频次：200[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/97980
专题	温州医科大学
作者单位	1.Rutgers Biomedical and Health Sciences; 2.Stony Brook University; 3.Wenzhou Medical University; 4.Rutgers New Jersey Medical School
推荐引用方式 GB/T 7714	Lu, Bin,Lee, Jae,Nie, Xiaobo,et al. Phosphorylation of Human TFAM in Mitochondria Impairs DNA Binding and Promotes Degradation by the AAA⁺ Lon Protease[J]. Molecular Cell,2013,49(1):121-132.
APA	Lu, Bin., Lee, Jae., Nie, Xiaobo., Li, Min., Morozov, Yaroslav I.., ... & Suzuki, Carolyn K.. (2013). Phosphorylation of Human TFAM in Mitochondria Impairs DNA Binding and Promotes Degradation by the AAA⁺ Lon Protease. Molecular Cell, 49(1), 121-132.
MLA	Lu, Bin,et al."Phosphorylation of Human TFAM in Mitochondria Impairs DNA Binding and Promotes Degradation by the AAA⁺ Lon Protease".Molecular Cell 49.1(2013):121-132.