Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease.
Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease.
复制标题
线粒体中人类TFAM的磷酸化会损害DNA的结合并促进AAA+ LON蛋白酶的降解。
DOI：
10.1016/j.molcel.2012.10.023
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发表时间：
2013-01-10
期刊：
影响因子：
16
通讯作者：
Suzuki, Carolyn K.
中科院分区：
文献类型：
--
作者：
Lu, Bin;Lee, Jae;Nie, Xiaobo;Li, Min;Morozov, Yaroslav I.;Venkatesh, Sundararajan;Bogenhagen, Daniel F.;Temiakov, Dmitry;Suzuki, Carolyn K.
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 post-translational 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 anti-cancer drug bortezomib. In cells with normal mtDNA levels, HMG1-phosphorylated TFAM is degraded by Lon. However in cells with severe mtDNA deficits, non-phosphorylated TFAM is also degraded as it is DNA-free. Depleting Lon in these cells increases TFAM, and upregulates mtDNA content, albeit transiently. Phosphorylation and proteolysis thus provide mechanisms for rapidly fine-tuning TFAM function and abundance in mitochondria, which are crucial for maintaining and expressing mtDNA.
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影响因子：
3.5
作者：
Ekstrand, MI;Falkenberg, M;Larsson, NG
通讯作者：
Larsson, NG
影响因子：
11.2
作者：
Guo J;Zheng L;Liu W;Wang X;Wang Z;Wang Z;French AJ;Kang D;Chen L;Thibodeau SN;Liu W
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DOI：
10.1016/j.bbabio.2010.10.023
发表时间：
2011-06
期刊：
Biochimica et biophysica acta
影响因子：
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Chandra D;Singh KK
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14.9
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通讯作者：
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