Nitric Oxide-Mediated Antioxidative Mechanism in Yeast through the Activation of the Transcription Factor Mac1

Nasuno, Ryo; Aitoku, Miho; Manago, Yuki; Nishimura, Akira; Sasano, Yu; Takagi, Hiroshi

doi:10.1371/journal.pone.0113788

Cited by 44 publications

(26 citation statements)

References 47 publications

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“…From the results of the nitrosative stress tolerance analyses, Δrib1 cells showed higher sensitivity to the acidified NaNO 2 condition than WT cells, indicating that the physiological expression level of RIB1 contributes to nitrosative stress tolerance. This is in contrast with our previous microarray analysis 17 , which indicated that RIB1 www.nature.com/scientificreports www.nature.com/scientificreports/ is not induced by NO treatment. On the other hand, fHb, one of the major NO detoxifying enzymes, is upregulated after exposure to NO through the activation of the transcription factor Fzf1 in S. cerevisiae or Cta4 in Candida albicans [31][32][33] .…”

Section: Discussioncontrasting

confidence: 99%

“…A low level of NO also plays a role in oxidative stress tolerance in bacteria 15 . In the budding yeast Saccharomyces cerevisiae, we found that NO confers high temperature stress tolerance through the activation of the copper-related transcription factor Mac1 [16][17][18] . On the other hand, an excessive level of RNS including NO could cause nitrosative stress leading to cellular damage or death.…”

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A Novel Mechanism for Nitrosative Stress Tolerance Dependent on GTP Cyclohydrolase II Activity Involved in Riboflavin Synthesis of Yeast

Anam

Nasuno

2020

Sci Rep

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The biological functions of nitric oxide (NO) depend on its concentration, and excessive levels of NO induce various harmful situations known as nitrosative stress. Therefore, organisms possess many kinds of strategies to regulate the intracellular no concentration and/or to detoxify excess no. Here, we used genetic screening to identify a novel nitrosative stress tolerance gene, RIB1, encoding GTP cyclohydrolase II (GTPCH2), which catalyzes the first step in riboflavin biosynthesis. Our further analyses demonstrated that the GTPCH2 enzymatic activity of Rib1 is essential for RIB1-dependent nitrosative stress tolerance, but that riboflavin itself is not required for this tolerance. Furthermore, the reaction mixture of a recombinant purified Rib1 was shown to quench NO or its derivatives, even though formate or pyrophosphate, which are byproducts of the Rib1 reaction, did not, suggesting that the reaction product of Rib1, 2,5-diamino-6-(5-phospo-d-ribosylamino)-pyrimidin-4(3 H)-one (DARP), scavenges NO or its derivatives. Finally, it was revealed that 2,4,5-triamino-1H-pyrimidin-6-one, which is identical to a pyrimidine moiety of DARP, scavenged NO or its derivatives, suggesting that DARP reacts with n 2 o 3 generated via its pyrimidine moiety. Nitric oxide (NO) is a small signaling molecule that plays various roles in a number of biological processes 1,2. In mammalian cells, NO is generally produced by three different isoforms of NO synthase (NOS) from l-arginine and NADPH 3. NOS consists of the oxygenase domain responsible for oxidation of l-arginine and the reductase domain which transfers electrons from NADPH to the oxygenase domain 4. Some Gram-positive bacteria have enzymes called bacterial NOS (bNOS), which is homologous to the oxygenase domain of NOS, and which exerts its NOS activity via interaction with uncertain reductase proteins 5. On the other hand, nitrate and nitrite serve as NO sources in plants, in which nitrate and nitrite are reduced to NO by nitrate reductase and nitrite reductase, respectively 6. Nitrite is also reduced to NO by heme-containing proteins including hemoglobin or molybdopterin proteins such as xanthine oxidase via their nitrite reductase activity 7,8. Furthermore, reduction of nitrite to NO is also catalyzed by the mitochondrial respiratory activity complex III and/or IV 9. NO activates soluble guanylyl cyclase (sGC) by binding to the heme in sGC. Activated sGC releases cyclic GMP, which is a second messenger leading to the relaxation of smooth muscle cells in mammals 10. Additionally, NO induces the posttranslational modification of proteins, such as S-nitrosation. S-nitrosation is formed via the reaction of NO with thiyl radical or between NO + , which is one electron oxidized form of NO, and the thiol group of cysteine residues in the target protein 11. Thiol group also undergoes S-nitrosation via transnitrosation, in which NO + group is transferred from a sulfur atom in nitrosothiol compound to that in a target thiol compound. The NO-responsive transcription factor OxyR is a...

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Section: Discussioncontrasting

confidence: 99%

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confidence: 99%

A Novel Mechanism for Nitrosative Stress Tolerance Dependent on GTP Cyclohydrolase II Activity Involved in Riboflavin Synthesis of Yeast

Anam

Nasuno

2020

Sci Rep

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“…Interestingly, in our study, L-NAME increased the accumulation of superoxide radicals during AmB treatment, while decreasing the proliferative capacity of cells in the presence of AmB, and thus decreasing survival. It seems that a nitric oxide radical-dependent tolerance system is switched on upon AmB treatment in yeast, perhaps similar to the system recently described by Nasuno and colleagues [ 56 ]. In that study, a downstream pathway of nitric oxide radicals involved in high-temperature stress tolerance in yeast was unravelled.…”

Section: Discussionsupporting

confidence: 67%

“…In that study, a downstream pathway of nitric oxide radicals involved in high-temperature stress tolerance in yeast was unravelled. They showed that nitric oxide radicals activated the transcription factor Mac1 that on its turn induced the CTR1 gene and resulted in increased cellular copper levels, which then resulted in activation of Sod1, a superoxide dismutase [ 56 ]. Alternatively, it could also be that nitric oxide activates, potentially via S-nitrosylation, AmB tolerance pathways such as the yeast HOG pathway [ 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide‐Dependent Tolerance Pathway

Vriens

Kumar

Struyfs

et al. 2017

Oxidative Medicine and Cellular Longevity

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Amphotericin B (AmB) induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB-induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB's fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L-NAME was used to interfere with nitric oxide radical production. L-NAME increased and accelerated AmB-induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S-nitrosoglutathione inhibited AmB's action. Hence, superoxide radicals were important for AmB's fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L-NAME, pointing to the potential of AmB-L-NAME combination therapy to treat fungal infections.

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“…The CTR1 , CTR3, and FRE1 genes/proteins in the category of copper iron transport were significantly upregulated. These three genes are all regulated by transcription factor Mac1p [33], but the expression of MAC1 was not significantly regulated in either the transcriptome or the proteome. In addition to CTR1 , CTR3 , and FRE1 , other genes downstream of MAC1—FRE7 , IRC7, and REE1 showed various degrees of upregulation in the transcriptome and proteome (Fig.…”

Section: Resultsmentioning

confidence: 99%

Nitric oxide increases biofilm formation in Saccharomyces cerevisiae by activating the transcriptional factor Mac1p and thereby regulating the transmembrane protein Ctr1

Zheng

Chen

et al. 2019

Biotechnol Biofuels

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Background Biofilms with immobilized cells encased in extracellular polymeric substance are beneficial for industrial fermentation. Their formation is regulated by various factors, including nitric oxide (NO), which is recognized as a quorum-sensing and signal molecule. The mechanisms by which NO regulates bacterial biofilms have been studied extensively and deeply, but were rarely studied in fungi. In this study, we observed the effects of low concentrations of NO on biofilm formation in Saccharomyces cerevisiae. Transcriptional and proteomic analyses were applied to study the mechanism of this regulation. Results Adding low concentrations of NO donors (SNP and NOC-18) enhanced biofilm formation of S. cerevisiae in immobilized carriers and plastics. Transcriptional and proteomic analyses revealed that expression levels of genes regulated by the transcription factor Mac1p was upregulated in biofilm cells under NO treatment. MAC1 promoted yeast biofilm formation which was independent of flocculation gene FLO11 . Increased copper and iron contents, both of which were controlled by Mac1p in the NO-treated and MAC1 -overexpressing cells, were not responsible for the increased biofilm formation. CTR1 , one out of six genes regulated by MAC1 , plays an important role in biofilm formation. Moreover, MAC1 and CTR1 contributed to the cells’ resistance to ethanol by enhanced biofilm formation. Conclusions These findings suggest that a mechanism for NO-mediated biofilm formation, which involves the regulation of CTR1 expression levels by activating its transcription factor Mac1p, leads to enhanced biofilm formation. The role of CTR1 protein in yeast biofilm formation may be due to the hydrophobic residues in its N-terminal extracellular domain, and further research is needed. This work offers a possible explanation for yeast biofilm formation regulated by NO and provides approaches controlling biofilm formation in industrial immobilized fermentation by manipulating expression of genes involved in biofilm formation. Electronic supplementary material The online version of this article (10.1186/s13068-019-1359-1) contains supplementary material, which is available to authorized users.

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Nitric Oxide-Mediated Antioxidative Mechanism in Yeast through the Activation of the Transcription Factor Mac1

Cited by 44 publications

References 47 publications

A Novel Mechanism for Nitrosative Stress Tolerance Dependent on GTP Cyclohydrolase II Activity Involved in Riboflavin Synthesis of Yeast

A Novel Mechanism for Nitrosative Stress Tolerance Dependent on GTP Cyclohydrolase II Activity Involved in Riboflavin Synthesis of Yeast

Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide‐Dependent Tolerance Pathway

Nitric oxide increases biofilm formation in Saccharomyces cerevisiae by activating the transcriptional factor Mac1p and thereby regulating the transmembrane protein Ctr1

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