title: Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe.
abstract: In the fission yeast Schizosaccharomyces pombe, we found that the putative NO dioxygenase SPAC869.02c (named Yhb1) and the S-nitrosoglutathione reductase Fmd2 cooperatively reduced intracellular NO levels as NO-detoxification enzymes. Although both mRNA and protein levels were increased with exogenous NO, their expression patterns were different during growth phases. While treatment with an NO synthase inhibitor in the log phase abrogated both NO production and Yhb1 expression, induction of Fmd2 in the stationary phase was correlated with elevated mitochondrial respiratory chain (MRC) activity, confirmed by the fact that inhibition of MRC complex III led to a decrease in Fmd2 and NO levels. Moreover, NO was localized in the mitochondria in the stationary phase, suggesting that there are two distinctive types of NO signaling in S. pombe. For mitochondria, pretreatment with an NO donor rescued cell growth by repressing generation of reactive oxygen species (ROS) under oxidative stress. DNA microarray analysis revealed that exogenous NO contributes to tolerance to hydrogen peroxide (H2O2) by (i) inhibition of Fe(3+) to Fe(2+) conversion, (ii) upregulation of the H2O2-detoxifying enzymes, and (iii) downregulation of the MRC genes, suggesting that NO plays a pivotal role in the negative feedback system to regulate ROS levels in S. pombe.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
authors.forename: Rika Indri
authors.initials: RI
authors.lastname: Astuti
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: D025461:Feedback, Physiological; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006861:Hydrogen Peroxide
keywords: Fenton reaction; Mitochondrial respiratory chain; Nitric oxide; Nitric oxide synthase; Reactive oxygen species; Schizosaccharomyces pombe; Yeast