Human prohibitin 1 maintains the organization and stability of the mitochondrial nucleoids
Human prohibitin 1 maintains the organization and stability of the mitochondrial nucleoids
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DOI：
10.1016/j.yexcr.2008.01.005
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发表时间：
2008-03-10
影响因子：
3.7
通讯作者：
Endo, Hitoshi
中科院分区：
文献类型：
--
作者：
Kasashima, Katsumi;Sumitani, Megumi;Endo, Hitoshi
线粒体禁止蛋白（PHB）具有多种功能，如调节细胞凋亡和维持线粒体形态。在这项研究中，我们阐明了一种新的线粒体功能，即PHB1调节线粒体DNA （mtDNA）的组织和维护。在phb1敲低的细胞中，我们发现mtDNA不被荧光染料染色，如溴化乙啶和PicoGreen，尽管线粒体膜电位仍然保持。我们还证明，从正常线粒体分离时主要存在于np -40不溶性部分的mtDNA，从phb1敲低的细胞分离时部分释放到可溶部分，这表明线粒体类核的组织已经改变。此外，我们发现PHB1通过稳定线粒体类核的已知蛋白质成分TFAM蛋白来调节mtDNA的拷贝数。然而，在phb1敲低的细胞中观察到，TFAM不影响mtDNA的组织。综上所述，这些结果表明PHB1通过tfam独立和tfam依赖的途径维持mtDNA的组织和拷贝数。(C) 2008爱思唯尔公司版权所有。
Mitochondrial prohibitin (PHB) proteins have diverse functions, such as the regulation of apoptosis and the maintenance of mitochondrial morphology. In this study, we clarified a novel mitochondrial function of PHB1 that regulates the organization and maintenance of mitochondrial DNA (mtDNA). In PHB1-knockdown cells, we found that mtDNA is not stained by fluorescent dyes, such as ethidium bromide and PicoGreen, although the mitochondrial membrane potential still maintains. We also demonstrated that mtDNA, which is predominantly found in the NP-40-insoluble fraction when isolated from normal mitochondria, is partially released into the soluble fraction when isolated from PHB1-knockdown cells, indicating that the organization of the mitochondrial nucleoids has been altered. Furthermore, we found that PHB1 regulates copy number of mtDNA by stabilizing TFAM protein, a known protein component of the mitochondrial nucleoids. However, TFAM does not affect the organization of mtDNA as observed in PHB1-knockdown cells. Taken together, these results demonstrate that PHB1 maintains the organization and copy number of the mtDNA through both TFAM-independent and -dependent pathways. (C) 2008 Elsevier Inc. All rights reserved.