title: Uptake of L-cystine via an ABC transporter contributes defense of oxidative stress in the L-cystine export-dependent manner in Escherichia coli.
abstract: Intracellular thiols like L-cystine and L-cystine play a critical role in the regulation of cellular processes. Here we show that Escherichia coli has two L-cystine transporters, the symporter YdjN and the ATP-binding cassette importer FliY-YecSC. These proteins import L-cystine, an oxidized product of L-cystine from the periplasm to the cytoplasm. The symporter YdjN, which is expected to be a new member of the L-cystine regulon, is a low affinity L-cystine transporter (Km = 1.1 μM) that is mainly involved in L-cystine uptake from outside as a nutrient. E. coli has only two L-cystine importers because ΔydjNΔyecS mutant cells are not capable of growing in the minimal medium containing L-cystine as a sole sulfur source. Another protein YecSC is the FliY-dependent L-cystine transporter that functions cooperatively with the L-cystine transporter YdeD, which exports L-cystine as reducing equivalents from the cytoplasm to the periplasm, to prevent E. coli cells from oxidative stress. The exported L-cystine can reduce the periplasmic hydrogen peroxide to water, and then generated L-cystine is imported back into the cytoplasm via the ATP-binding cassette transporter YecSC with a high affinity to L-cystine (Km = 110 nM) in a manner dependent on FliY, the periplasmic L-cystine-binding protein. The double disruption of ydeD and fliY increased cellular levels of lipid peroxides. From these findings, we propose that the hydrogen peroxide-inducible L-cystine/L-cystine shuttle system plays a role of detoxification of hydrogen peroxide before lipid peroxidation occurs, and then might specific prevent damage to membrane lipids.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohtsu
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Morigasaki
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Saiki
authors.affiliation: Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Company, Kawasaki, Kanagawa, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Company, Kawasaki, Kanagawa, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nonaka
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takagi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000220:Adaptation, Biological; D001692:Biological Transport; D003553:Cystine / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D023061:Gene Order; D005798:Genes, Bacterial; D056426:Genetic Loci; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation; D008563:Membrane Lipids / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D018384:Oxidative Stress
chemical_list: D018528:ATP-Binding Cassette Transporters; D008563:Membrane Lipids; D003553:Cystine; D006861:Hydrogen Peroxide
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