title: Mitochondrial and cytoplasmic thioredoxin reductase variants encoded by a single Drosophila gene are both essential for viability.
abstract: Defense against oxidative stress in mammals includes the regeneration of the major thiol reductants glutathione and thioredoxin by glutathione reductase and thioredoxin reductase (TrxR), respectively. In contrast, Drosophila, and possibly insects in general, lacks glutathione reductase and must rely solely on the TrxR system. The mammalian TrxRs described so far are selenoproteins that utilize NADPH to reduce protein as well as nonprotein substrates in mitochondria and cytoplasm of cells. We show that a single Drosophila gene, Trxr-1, encodes non-selenocysteine-containing cytoplasmic and mitochondrial TrxR isoforms that differ with respect to their N termini. We generated transcript-specific mutants and used in vivo approaches to explore the biological functions of the two enzyme variants by introducing the corresponding transgenes into different Trxr-1 mutants. The results show that, although the two TrxR isoforms have similar biochemical properties, their biological functions are not interchangeable.
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg, 37077 Göttingen, Germany.
authors.forename: Fanis
authors.initials: F
authors.lastname: Missirlis
authors.forename: Julia K
authors.initials: JK
authors.lastname: Ulschmid
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Hirosawa-Takamori
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grönke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schäfer
authors.forename: Katja
authors.initials: K
authors.lastname: Becker
authors.forename: John P
authors.initials: JP
authors.lastname: Phillips
authors.forename: Herbert
authors.initials: H
authors.lastname: Jäckle
mesh_terms: D000818:Animals; D001483:Base Sequence; D003593:Cytoplasm / Q000201:enzymology*; D017931:DNA Primers; D004330:Drosophila / Q000201:enzymology / Q000235:genetics*; D007700:Kinetics; D008136:Longevity / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology*; D009154:Mutation; D018384:Oxidative Stress; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D013880:Thioredoxin-Disulfide Reductase