title: Redox-dependent Regulation of Gluconeogenesis by a Novel Mechanism Mediated by a Peroxidatic Cysteine of Peroxiredoxin.
abstract: Peroxiredoxin is an abundant peroxidase, but its non-peroxidase function is also important. In this study, we discovered that Tsa1, a major peroxiredoxin of budding yeast cells, is required for the efficient flux of gluconeogenesis. We found that the suppression of pyruvate kinase (Pyk1) via the interaction with Tsa1 contributes in part to gluconeogenic enhancement. The physical interactions between Pyk1 and Tsa1 were augmented during the shift from glycolysis to gluconeogenesis. Intriguingly, a peroxidatic cysteine in the catalytic center of Tsa1 played an important role in the physical Tsa1-Pyk1 interactions. These interactions are enhanced by exogenous H2O2 and by endogenous reactive oxygen species, which is increased during gluconeogenesis. Only the peroxidatic cysteine, but no other catalytic cysteine of Tsa1, is required for efficient growth during the metabolic shift to obtain maximum yeast growth (biomass). This Tsa1 function is separable from the peroxidase function as an antioxidant. This is the first report to demonstrate that peroxiredoxin has a novel nonperoxidase function as a redox-dependent target modulator and that pyruvate kinase is modulated via an alternative mechanism.
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Irokawa
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-0861, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tachibana
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Matsuyama
authors.affiliation: Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ogasawara
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Iwai
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-0861, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Kuge
mesh_terms: D018533:Biomass; D003545:Cysteine / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D055432:Metabolomics; D010084:Oxidation-Reduction / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014199:Trehalose / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D006003:Glycogen; D014199:Trehalose; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D009195:Peroxidase; D005947:Glucose; D003545:Cysteine