Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster

Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster
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DOI:
10.1016/j.bbrc.2012.11.084
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发表时间:
2013-01-11
影响因子:
3.1
通讯作者:
Matsuura, Etsuko T.
Matsuura, Etsuko T.
中科院分区:
生物学4区
文献类型:
--
作者:
Matsuda, Takako;Kanki, Tomotake;Matsuura, Etsuko T.

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线粒体转录因子A(TFAM)通过包装线粒体DNA,形成线粒体类核,在线粒体DNA(mtDNA)的维持中发挥作用。关于TFAM在细胞水平上的功能已有许多报道,但在个体生物体中进行的研究很少。在这里,我们研究TFAM对果蝇寿命和氧化应激反应的影响,通过使用GAL4/UAS系统过表达TFAM。在标准条件下,TFAM过表达果蝇的寿命比对照果蝇短。然而,TFAM过表达的苍蝇的寿命更长,当他们与1%H2O2处理。这些结果表明,尽管过量的TFAM对寿命有负面影响,但它在强氧化应激下具有防御功能。在TFAM过表达的果蝇中,未观察到mtDNA拷贝数或mtDNA转录的显著变化。然而,总抗氧化活性测定的结果表明TFAM参与消除氧化应激的可能性。目前的结果清楚地表明TFAM过表达对果蝇的寿命在标准条件下和氧化应激条件下的影响,我们的研究结果有助于理解涉及TFAM在线粒体中的生理机制。(C)2012 Elsevier Inc. All rights reserved.
Mitochondrial transcription factor A (TFAM) plays a role in the maintenance of mitochondrial DNA (mtDNA) by packaging mtDNA, forming the mitochondrial nucleoid. There have been many reports about a function of TFAM at the cellular level, but only a few studies have been done in individual organisms. Here we examined the effects of TFAM on the Drosophila lifespan and oxidative stress response, by overexpressing TFAM using the GAL4/UAS system. Under standard conditions, the lifespan of TFAM-overexpressing flies was shorter than that of the control flies. However, the lifespan of TFAM-overexpressing flies was longer when they were treated with 1% H2O2. These results suggest that even though excess TFAM has a negative influence on lifespan, it has a defensive function under strong oxidative stress. In the TFAM-overexpressing flies, no significant changes in mtDNA copy number or mtDNA transcription were observed. However, the results of a total antioxidant activity assay suggest the possibility that TFAM is involved in the elimination of oxidative stress. The present results clearly show the effects of TFAM overexpression on the lifespan of Drosophila under both standard conditions and oxidative stress conditions, and our findings contribute to the understanding of the physiological mechanisms involving TFAM in mitochondria. (C) 2012 Elsevier Inc. All rights reserved.