Human prohibitin 1 maintains the organization and stability of the mitochondrial nucleoids

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• 作者：Katsumi Kasashima ; Megumi Sumitani ; Masaaki Satoh ; Hitoshi Endo
• 关键词：Mitochondria ; Mitochondrial DNA ; Prohibitin ; Mitochondrial nucleoid ; TFAM
• 刊名：Experimental Cell Research
• 出版年：2008
• 出版时间：10 March 2008
• 年：2008
• 卷：314
• 期：5
• 页码：988-996
• 全文大小：973 K

文摘

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.