Nucleoid localization of Hsp40 Mdj1 is important for its function in maintenance of mitochondrial DNA.
Nucleoid localization of Hsp40 Mdj1 is important for its function in maintenance of mitochondrial DNA.
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DOI：
10.1016/j.bbamcr.2013.05.012
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发表时间：
2013-10
影响因子：
5.1
通讯作者：
Craig, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Ciesielski, Grzegorz L.;Plotka, Magdalena;Manicki, Mateusz;Schilke, Brenda A.;Dutkiewicz, Rafal;Sahi, Chandan;Marszalek, Jaroslaw;Craig, Elizabeth A.
线粒体DNA（mtDNA）的忠实复制和繁殖对细胞呼吸至关重要。分子伴侣是一种普遍存在的蛋白质，参与蛋白质的折叠和蛋白质复合物的重塑，与线粒体DNA的相互作用密切相关。特别是，缺乏Mdj 1（线粒体基质中Hsp 70的Hsp 40共伴侣）的细胞不能维持功能性mtDNA。在这里，我们报告说，Mdj 1的绝大多数是与类核，DNA-蛋白质复合物，是线粒体DNA交易的功能单位。强调的重要性，Hsp 70分子伴侣活性在维持mtDNA，Mdj 1变异体具有改变的Hsp 70相互作用的J-结构域不维持mtDNA。然而，一个J-域包含片段的水平，Mdj 1是正常存在的是不能维持线粒体DNA，这表明Mdj 1的功能超出了它的J-域进行。然而，当J结构域过表达时，Mdj 1缺失后mtDNA功能的丧失被延迟。Mdj 1变体的分析揭示了类核缔合和DNA维持活性之间的相关性，表明定位在功能上是重要的。我们发现Mdj 1具有DNA结合活性，保留DNA结合活性的变体也保留了类核缔合。总之，我们的研究结果是一致的模型，其中Mdj 1，拴系到类核通过DNA结合，从而驱动一个高的局部浓度的热休克蛋白70机器，是重要的忠实的DNA维护和繁殖。J蛋白辅助分子伴侣Mdj 1是维持mtDNA功能的关键。大多数Mdj 1定位于类核，可能通过与mtDNA相互作用。Mdj 1的类核定位对于线粒体DNA的维持是必要的。Mdj 1在线粒体DNA维持中的功能需要与Hsp 70的协同作用。
Faithful replication and propagation of mitochondrial DNA (mtDNA) is critical for cellular respiration. Molecular chaperones, ubiquitous proteins involved in protein folding and remodeling of protein complexes, have been implicated in mtDNA transactions. In particular, cells lacking Mdj1, an Hsp40 co-chaperone of Hsp70 in the mitochondrial matrix, do not maintain functional mtDNA. Here we report that the great majority of Mdj1 is associated with nucleoids, DNA-protein complexes that are the functional unit of mtDNA transactions. Underscoring the importance of Hsp70 chaperone activity in the maintenance of mtDNA, an Mdj1 variant having an alteration in the Hsp70-interacting J-domain does not maintain mtDNA. However, a J-domain containing fragment expressed at the level that Mdj1 is normally present is not competent to maintain mtDNA, suggesting a function of Mdj1 beyond that carried out by its J-domain. Nevertheless, loss of mtDNA function upon Mdj1 depletion is retarded when the J-domain, is overexpressed. Analysis of Mdj1 variants revealed a correlation between nucleoid association and DNA maintenance activity, suggesting that localization is functionally important. We found that Mdj1 has DNA binding activity and that variants retaining DNA-binding activity also retained nucleoid association. Together, our results are consistent with a model in which Mdj1, tethered to the nucleoid via DNA binding, thus driving a high local concentration of the Hsp70 machinery, is important for faithful DNA maintenance and propagation. J-protein co-chaperone Mdj1 is critical for maintenance of functional mtDNA. Majority of Mdj1 localizes to the nucleoid, likely via interaction with mtDNA. Nucleoid localization of Mdj1 is necessary for mtDNA maintenance. Function of Mdj1 in mtDNA maintenance requires cooperation with Hsp70.
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DOI：
10.1073/pnas.85.18.6632
发表时间：
1988-09-01
影响因子：
11.1
作者：
LIBEREK, K;GEORGOPOULOS, C;ZYLICZ, M
通讯作者：
ZYLICZ, M
影响因子：
4.8
作者：
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影响因子：
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作者：
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通讯作者：
Bukau, B
DOI：
10.1083/jcb.123.1.109
发表时间：
1993-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gambill BD;Voos W;Kang PJ;Miao B;Langer T;Craig EA;Pfanner N
通讯作者：
Pfanner N
影响因子：
4.8
作者：
Bird, Jeremy G.;Sharma, Suveena;Wickner, Sue
通讯作者：
Wickner, Sue