title: Regulatory mechanism of the flavoprotein Tah18-dependent nitric oxide synthesis and cell death in yeast.
abstract: Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. The regulatory mechanism of NO generation in unicellular eukaryotic yeast cells is poorly understood due to the lack of mammalian and bacterial NO synthase (NOS) orthologues, even though yeast produces NO under oxidative stress conditions. Recently, we reported that the flavoprotein Tah18, which was previously shown to transfer electrons to the iron-sulfur cluster protein Dre2, is involved in NOS-like activity in the yeast Saccharomyces cerevisiae. On the other hand, Tah18 was reported to promote apoptotic cell death after exposure to hydrogen peroxide (H2O2). Here, we showed that NOS-like activity requiring Tah18 induced cell death upon treatment with H2O2. Our experimental results also indicate that Tah18-dependent NO production and cell death are suppressed by enhancement of the interaction between Tah18 and its molecular partner Dre2. Our findings indicate that the Tah18-Dre2 complex regulates cell death as a molecular switch via Tah18-dependent NOS-like activity in response to environmental changes.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nasuno
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kawahara
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan. Electronic address: hiro@bs.naist.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takagi
mesh_terms: D016923:Cell Death; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007506:Iron-Sulfur Proteins / Q000502:physiology; D046912:Multiprotein Complexes / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
chemical_list: C531900:Dre2 protein, S cerevisiae; D007506:Iron-Sulfur Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C552878:Tah18 protein, S cerevisiae; D019331:NG-Nitroarginine Methyl Ester
keywords: Cell death; Dre2; Nitric oxide; Nitric oxide synthase; Saccharomyces cerevisiae; Tah18; Yeast