title: Lifespan extension and paraquat resistance in a ubiquinone-deficient Escherichia coli mutant depend on transcription factors ArcA and TdcA.
abstract: 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.
authors.affiliation: Integrative and Evolutionary Biology, Department of Biological Sciences, University of Southern California, Los Angeles, 90089, USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Gonidakis
authors.forename: Steven E
authors.initials: SE
authors.lastname: Finkel
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005798:Genes, Bacterial; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D010269:Paraquat / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; C083450:TdcA protein, E coli; D015534:Trans-Activators; C041610:arcA protein, E coli; D014451:Ubiquinone; D008780:Methyltransferases; C019616:UbiG protein, E coli; D010269:Paraquat