Gonidakis Stavros, Finkel Steven E, Longo Valter D
Integrative and Evolutionary Biology, Department of Biological Sciences, University of Southern California, Los Angeles, 90089, USA.
Aging (Albany NY). 2011 Mar;3(3):291-303. doi: 10.18632/aging.100301.
We recently reported a genome-wide screen for extended stationary phase survival in Escherichia coli. One of the mutants recovered is deleted for ubiG, which encodes a methyltransferase required for the biosynthesis of ubiquinone. The ubiG mutant exhibits longer lifespan, as well as enhanced resistance to thermal and oxidative stress compared to wt at extracellular pH9. The longevity of the mutant, as well as its resistance to the superoxide-generating agent paraquat, is partially dependent on the hypoxia-inducible transcription factor ArcA. A microarray analysis revealed several genes whose expression is either suppressed or enhanced by ArcA in the ubiG mutant. TdcA is a transcription factor involved in the transport and metabolism of amino acids during anaerobic growth. Its enhanced expression in the ubiG mutant is dependent on ArcA. Our data are consistent with the hypothesis that ArcA and TdcA function in the same genetic pathway to increase lifespan and enhance oxidative stress resistance in the ubiG mutant. Our results might be relevant for the elucidation of the mechanism of lifespan extension in mutant mice and worms bearing mutations in ubiquinone biosynthetic genes.
我们最近报道了一项针对大肠杆菌延长稳定期存活的全基因组筛选。筛选出的突变体之一缺失了ubiG基因，该基因编码泛醌生物合成所需的甲基转移酶。与野生型相比，ubiG突变体在细胞外pH9条件下表现出更长的寿命，以及对热应激和氧化应激更强的抗性。该突变体的长寿及其对产生超氧化物的百草枯的抗性部分依赖于缺氧诱导转录因子ArcA。微阵列分析揭示了几个基因，其在ubiG突变体中的表达被ArcA抑制或增强。TdcA是一种参与厌氧生长期间氨基酸运输和代谢的转录因子。其在ubiG突变体中的表达增强依赖于ArcA。我们的数据与以下假设一致：ArcA和TdcA在同一遗传途径中发挥作用，以增加ubiG突变体的寿命并增强其抗氧化应激能力。我们的结果可能与阐明泛醌生物合成基因突变的突变小鼠和蠕虫的寿命延长机制有关。
