Inhibition of yeast glutathione reductase by trehalose: possible implications in yeast survival and recovery from stress

Sebollela, Adriano; Louzada, Paulo Roberto; Sola‐Penna, Mauro; Sarone-Williams, Verietta; Coelho‐Sampaio, Tatiana; Ferreira, Sérgio T.

doi:10.1016/j.biocel.2003.10.006

Cited by 47 publications

(31 citation statements)

References 30 publications

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“…The role of this simultaneous expression and functioning of biosynthetic and degradative machineries in metabolism is still controversial, and such futile cycles have been proposed both as metabolic mistakes and as key points in metabolic control (Hottiger et al, 1987;Mahmud et al, 2009). In the case of trehalose metabolism, having both machineries ready to use under the control of the very fast mechanisms of enzymic regulation could be the energetic payment for a suitable system to quickly accumulate trehalose when protection is needed, and then efficiently eliminate it, allowing fast recovery of cell growth after stress (Hottiger et al, 1987;Van Dijck et al, 1995;Singer & Lindquist, 1998b;Wera et al, 1999;Sebollela et al, 2004). Trehalose elimination is a determining factor in the resumption of normal growth due to its ability to interact with membranes and proteins.…”

Section: Discussionmentioning

confidence: 99%

The three trehalases Nth1p, Nth2p and Ath1p participate in the mobilization of intracellular trehalose required for recovery from saline stress in Saccharomyces cerevisiae

Garré

Matallana

2009

Microbiology

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Trehalose accumulation is a common response to several stresses in the yeast Saccharomyces cerevisiae. This metabolite protects proteins and membrane lipids from structural damage and helps cells to maintain integrity. Based on genetic studies, degradation of trehalose has been proposed as a required mechanism for growth recovery after stress, and the neutral trehalase Nth1p as the unique degradative activity involved. Here we constructed a collection of mutants for several trehalose metabolism and transport genes and analysed their growth and trehalose mobilization profiles during experiments of saline stress recovery. The behaviour of the triple Dnth1Dnth2Dath1 and quadruple Dnth1Dnth2Dath1Dagt1 mutant strains in these experiments demonstrates the participation of the three known yeast trehalases Nth1p, Nth2p and Ath1p in the mobilization of intracellular trehalose during growth recovery after saline stress, rules out the participation of the Agt1p H + -disaccharide symporter, and allows us to propose the existence of additional new mechanisms for trehalose mobilization after saline stress.

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Section: Discussionmentioning

confidence: 99%

The three trehalases Nth1p, Nth2p and Ath1p participate in the mobilization of intracellular trehalose required for recovery from saline stress in Saccharomyces cerevisiae

Garré

Matallana

2009

Microbiology

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“…Recent kinetic studies have shown that genes encoding trehalases should be induced at early stages of the stress response to allow quick return of trehalose concentration to the low level after the stress ceases (32). Rapid trehalose degradation is essential for stress recovery because the presence of high amounts of this metabolite, although advantageous under stress conditions, severely disrupts normal physiological functions (7).…”

Section: Analysis Of Expression Profiles Of Putative Crt1pmentioning

confidence: 99%

Identification of New Genes Regulated by the Crt1 Transcription Factor, an Effector of the DNA Damage Checkpoint Pathway in Saccharomyces cerevisiae

Zaim

Speina

Kierzek

2005

Journal of Biological Chemistry

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The Crt1 (RFX1) protein in Saccharomyces cerevisiae is an effector of the DNA damage checkpoint pathway. It recognizes a 13-bp cis-regulatory element in the 5 -untranslated region (5 -UTR) of the ribonucleotide reductase genes RNR2, RNR3, and RNR4; the HUG1 gene; and itself. We calculated the weight matrix representing the Crt1p binding site motif according to analysis of the 5 -UTR sequences of the genes that are under its regulation. We subsequently searched the 5 -UTR sequences of all the genes in the yeast genome for the occurrence of this motif. The motif was found in regulatory regions of 30 genes. A statistical analysis showed that it is unlikely that a random gene cluster contains the motif conserved as well as the Crt1p binding site. Analysis of microarray data provided supporting evidence for five putative Crt1p targets: FSH3, YLR345W, UBC5, NDE2, and NTH2. We used reverse transcription-PCR to compare the expression levels of these genes in wild-type and crt1⌬ strains. Our results indicated that FSH3, YLR345W, and NTH2 are indeed under the regulation of Crt1p. Sequence analysis of the FSH3p indicated that this protein may be involved in folate metabolism either by carrying serine hydrolase activity required for the novel metabolic pathway involving dihydrofolate reductase (DHFR) or by directly interacting with the DHFR enzyme. We postulate that Crt1p may influence deoxyribonucleotide synthesis not only by regulating expression of the RNR genes but also by modulating DHFR activity. FSH3p shares significant sequence similarity with the product of the human tumor suppressor gene OVCA2. YLR345Wp and NTH2p are enzymes involved in the central metabolism under stress conditions.

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“…The transcription of NTH1 is stress responsive (62); however, the activity of Nth1 is greater during recovery from stress (39), allowing Nth1 to successfully compete with the biosynthetic pathway and reduce intracellular trehalose levels (28). This degradation of trehalose is critical for recovery from heat shock (59) as very high levels of trehalose can interfere with normal protein activity by stabilizing proteins in nonnative conformations and inhibiting the refolding of these denatured proteins by HSPs (12,43,44,46,56). Taken together, these data have led to a temporal model of trehalose function as a cochaperone during the heat shock response: trehalose functions to protect proteins at the initial stages of the heat shock response before HSPs have been fully induced, but trehalose must be degraded in order for the HSPs to fully assist the cell in recovery from heat shock (47).…”

mentioning

confidence: 99%

The Natural Osmolyte Trehalose Is a Positive Regulator of the Heat-Induced Activity of Yeast Heat Shock Transcription Factor

Conlin

Nelson

2007

Molecular and Cellular Biology

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In Saccharomyces cerevisiae, the intracellular concentration of trehalose increases rapidly in response to many environmental stresses, including heat shock. These high trehalose levels have been correlated with tolerance to adverse conditions and led to the model that trehalose functions as a chemical cochaperone. Here, we show that the transcriptional activity of Hsf1 during the heat shock response depends on trehalose. Strains with low levels of trehalose have a diminished transcriptional response to heat shock, while strains with high levels of trehalose have an enhanced transcriptional response to heat shock. The enhanced transcriptional response does not require the other heat-responsive transcription factors Msn2/4 but is dependent upon heat and Hsf1. In addition, the phosphorylation levels of Hsf1 correlate with both transcriptional activity and the presence of trehalose. These in vivo results support a new role for trehalose, where trehalose directly modifies the dynamic range of Hsf1 activity and therefore influences heat shock protein mRNA levels in response to stress.Trehalose is a disaccharide of glucose that is found predominantly in bacteria, fungi (including yeasts), plants, and invertebrates. This natural osmolyte was initially characterized as a storage carbohydrate due to the high intracellular concentrations observed during these organisms' resting and anhydrobiotic states (reviewed in reference 55). Since these states involve the ability to survive stressful conditions, trehalose levels were then linked to thermotolerance, the ability of an organism to survive an otherwise lethal heat shock (reviewed in reference 47). Trehalose has been shown to stabilize the structures and enzymatic activities of proteins against thermal denaturation in vitro (15,27,63). In addition, trehalose can prevent the aggregation of misfolded proteins, including amyloidogenic proteins (3,11,27,33,46,52), and is being considered for clinical trials for Huntington's disease (53). Trehalose is more effective than other sugars in protecting proteins against thermal denaturation and aggregation because of its unusual ability to alter the water environment surrounding a protein, stabilizing the protein in its native conformation (1,30,34,48).In the yeast Saccharomyces cerevisiae, trehalose levels vary depending on the environment of the cell. The levels are almost undetectable during normal exponential growth. After heat shock, trehalose levels increase rapidly and dramatically, along with the accumulation of heat shock proteins (HSPs) (26,28). This rapid increase in trehalose has been attributed to the increase in both the translation of the genes involved in the synthesis of trehalose (TPS1 and TPS2) (4, 41, 58) and the substrates required for trehalose synthesis (1, 61). In addition, the enzymatic activity of TPS1 increases during the heat shock response (1, 38). High trehalose levels can stabilize enzymatic activity and can prevent the aggregation of exogenous proteins in vivo during heat shock (45,46). Trehalose is d...

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Inhibition of yeast glutathione reductase by trehalose: possible implications in yeast survival and recovery from stress

Cited by 47 publications

References 30 publications

The three trehalases Nth1p, Nth2p and Ath1p participate in the mobilization of intracellular trehalose required for recovery from saline stress in Saccharomyces cerevisiae

The three trehalases Nth1p, Nth2p and Ath1p participate in the mobilization of intracellular trehalose required for recovery from saline stress in Saccharomyces cerevisiae

Identification of New Genes Regulated by the Crt1 Transcription Factor, an Effector of the DNA Damage Checkpoint Pathway in Saccharomyces cerevisiae

The Natural Osmolyte Trehalose Is a Positive Regulator of the Heat-Induced Activity of Yeast Heat Shock Transcription Factor

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