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Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid

Sergio Giannattasio, Nicoletta Guaragnella, Maša Ždralević and 1 more

Frontiers in Microbiology · 2013

doi:10.3389/fmicb.2013.00033

Abstract

Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 26, 2026. Paragraph numbers are ours, so an answer can point at one.

INTRODUCTION

Acetic acid is a stress and death inducing agent produced en route to alcoholic fermentation carried out by Saccharomyces cerevisiae. Acetic acid can have negative effects in industrial fermentation processes such as wine production, negatively affecting wine quality, or lignocellulosic fermentations for bioethanol production underpinning its biotechnological relevance. For example, acetic acid concentration in grape must and wine may vary from 4 to even 80 mM, depending on its microbial origins. Acetic acid is also a food preservative and the resistance of some yeast species to this compound can be associated with food spoilage causing major economic losses in the food industries. Thus the elucidation of the stress resistance and cell death mechanisms induced by acetic acid in yeast can impact the design of strategies for improving fermentations or decrease the food spoilage by acetic acid resistant-yeast species.

On the other hand, a fundamental aspect of acetic acid stress response is related to the capacity of the model organism S. cerevisiae to cope with newly encountered environmental conditions. Yeast may adapt and survive with alternatives in their genome expression and metabolism and is one of the most thoroughly studied unicellular eukaryotes at the cellular, molecular, and genetic level due to its well-known experimental tractability. Evidence has also been gathered showing that S. cerevisiae is able to undergo a programmed cell death (PCD) process triggered by different internal and external stimuli including acetic acid. Such findings provide new tools and a model for cell death research at the molecular level. It is of note that mortality induced by acetic acid which accumulates in the culture medium has been proposed to participate in the mechanism of chronological aging in yeast; accordingly, buffering the medium to pH 6–7 significantly extends chronological life span.

In this review we elaborate on current knowledge on the mechanisms of toxicity and tolerance to acetic acid stress obtained in the model eukaryote S. cerevisiae.

ACETIC ACID STRESS AND YEAST ADAPTATION

Like other weak acids, acetic acid displays increased antimicrobial action at low pH (<pKa = 4.76) in the undissociated state. At pH 4.5 the uncharged molecules enter cells primarily by facilitated diffusion through the Fps1p aquaglyceroporin channel, encounter a more neutral pH in the cytoplasm and dissociate into acetate and protons (Figure 1). The protons lead to cytoplasmic acidification thereby inhibiting important metabolic processes. Weak acids induce activation of the proton-translocating ATPase Pma1p in yeast plasma membrane, which pumps out the protons generated by weak acid dissociation in the cytosol in an ATP-dependent manner. This ensures maintenance of the electrochemical potential across plasma membrane regulating ion and pH balance and providing energy for nutrient uptake.

However, the differences in weak acid toxicity appear to mirror major differences existing in the transport and metabolism of the weak acid in yeast cells. Differently from sorbic and benzoic acid, which cannot be metabolized by S. cerevisiae and act as membrane-damaging substances causing severe oxidative stress under aerobic conditions, acetic acid can be used as the sole carbon and energy source by S. cerevisiae and is not toxic under such conditions. Thus, S. cerevisiae cells are normally able to grow on acetic acid medium. Under this condition the weak acid is found in a dissociated form and acetate is transported across the plasma membrane either through an electroneutral proton symport transporter, encoded by ADY2 or the monocarboxylate transporter encoded by JEN1. Acetate taken up by cells is converted to acetyl-CoA by one of either peroxisomal or cytosolic acetyl-CoA synthetases. Acetyl-CoA is then consumed in the glyoxylate shunt or oxidized in mitochondria through the tricarboxylic acid cycle (;, and references Therein). However, typical S. cerevisiae cells grown on glucose cannot metabolize acetic acid due to the activation of glucose repression pathways. Thus, yeast is sensitive to acetic acid stress in the presence of glucose. Acetate transport, as its metabolism, is also under glucose repression in S. cerevisiae but not in Zygosaccharomyces bailii that can metabolize acetic acid in the presence of glucose and is known for its high resistance to weak acids in glucose-containing media.

In glucose-containing media at pH 4.5 yeast cells can activate an adaptive response to weak acids, and resume to grow after a lag phase. Mechanisms of yeast adaptation to most common monocarboxylate preservatives mainly involve plasma membrane transporters and proton-translocating ATPase. Plasma membrane transporter Pdr12p, a member of ATP-binding cassette (ABC)-transporter family was strongly induced by sorbic, benzoic acid, and certain other moderately lipophilic carboxylate compounds, and to a lesser extent by acetic acid. The accumulation of Pdr12p in the plasma membrane, dependent on War1p transcription factor (see below), increases weak acid resistance mediating cellular extrusion of weak acid anion.

Transcription factor Haa1p is required for a rapid yeast adaptation to acetic and propionic acids (; Figure 1). In particular, Haa1p, directly or indirectly, specifically regulates approximately 80% of the acetic acid-induced gene expression. Among the Haa1p regulon, elimination of HRK1 and, to a lower extent, of SAP30 gene, led to the strongest susceptibility phenotypes to acetic acid, the first gene encoding a protein kinase possibly involved in the reduction of intracellular acetate concentration and the latter encoding a component of the Rpdl3L histone deacetylase complex involved in the epigenetic regulation of yeast transcriptional response to acetic acid stress. Other transcription factors which are known to orchestrate weak acid stress response in yeast including Msn2p/Msn4p and Rim101p, regulate only a few number of acetic acid-tolerance gene transcription.

Unlike the sorbic acid stress, in which a gain of function of Pdr12p transporter is involved in the acid resistance through PDR12 up-regulation, adaptation to acetic acid involves a loss of function ( and references therein) of Fps1p aquaglyceroporin (Figure 1). Acetic acid challenge at low pH causes activation of two mitogen-activated protein (MAP) kinases, Hog1p, involved in the high-osmolarity glycerol (HOG) signaling pathway and Slt2p involved in cell wall integrity pathway. Hog1p-dependent phosphorylation of Fps1p results in its ubiquitination, endocytosis, and final degradation in the vacuole. Therefore, in a weak-acid specific manner, the Hog1p-directed destabilization of Fps1p eliminates the route for acetic acid entry into the cell, generating a resistance to varied levels of acetic acid.

Such acetic acid stress response is different from hyperosmotic stress adaptation. At pH 6.8 on glucose medium cultures, very high concentrations of acetate anion (500 mM) inhibit yeast cell growth inducing a typical HOG response to sodium acetate salt stress with up-regulation of the expression of GPD1, encoding glycerol-3-phosphate dehydrogenase, and increased intracellular glycerol level to counteract hyperosmotic stress. At pH 4.5 a much lower acetic acid level (100 mM) is needed to cause comparable growth inhibition, with GPD1 transcript displaying only a slight, transient induction and declining of intracellular glycerol. Yet, the transcription factors Gis1p and Rph1p, regulating glycerol and acetate metabolism, have been shown to function downstream of TOR, RAS/cAMP, and AKT/SCH9 pathways in extending the lifespan of nutrient restricted yeast cells.

ACETIC ACID-INDUCED PROGRAMMED CELL DEATH

Depending on their concentrations as well as on their lipophilic moiety, weak acids may cause delay of microbial cell growth, cytostasis, or cell death. Less lipophilic acetic acid under certain conditions, compromises cell viability leading cells to death.

The yeast S. cerevisiae undergoes a PCD process in response to lethal concentrations of acetic acid. Recent achievements in the characterization of cell components and mechanisms involved in yeast acetic acid-induced PCD (AA-PCD) are reported below (Figure 1).

Since the discovery of a yeast mutant exhibiting apoptosis hallmarks, S. cerevisiae has been established as an ideal model system to study PCD pathways due to the high level of phylogenetic conservation of biochemical pathways and regulators between yeast and mammals. Yeast PCD shares most of the morphological and biochemical hallmarks of mammalian apoptosis, such as phosphatidylserine externalization to the outer layer of the cytoplasmic membrane, DNA fragmentation, chromatin condensation, reactive oxygen species (ROS) production as well as a pivotal role of mitochondria.

Exponentially growing S. cerevisiae cells undergo PCD when exposed to 80 mM acetic acid. Progressive loss of viable cells is complete after 200 min from AA-PCD induction. Consistently, AA-PCD cells showed early chromatin condensation with intact plasma membrane together with ribosomal RNA degradation; nuclear DNA fragmentation ensues, with the maximum percentage at 150 min. The earliest event (15 min) following acetic acid challenge is ROS production, with a different role for hydrogen eroxide and superoxide anion. Hydrogen peroxide appears to be a second messenger in AA-PCD cascade of events, as also shown by AA-PCD inhibition by ROS scavenger N-acetyl cysteine (NAC; ). ROS level en route to AA-PCD is modulated by the antioxidant enzymes catalase and superoxide dismutase (SOD), whose over-expression prevents and exacerbates AA-PCD, respectively.

Mitochondria are strongly implicated in AA-PCD. Following AA-PCD induction the release of cytochrome c (cyt c) starts at 60 min and reaches a maximum at 150 min. Cyt c is released from intact coupled mitochondria and once in the cytosol can function both as an electron donor and a ROS scavenger. Later in AA-PCD released cyt c is degraded, possibly by yet unidentified proteases and mitochondria become gradually uncoupled as judged by a decrease of the respiratory control index (RCI), a collapse of the mitochondrial membrane potential, a reduction in cyt c oxidase (COX) activity and in cytochromes a–a3 levels. Studies on ADP/ATP carrier, YCA1 and cyt c knock-out cells have revealed that AA-PCD can also occur without cyt c release, but with a lower death rate compared to wild type cells. Studies on mutant cells expressing a stable but catalytically inactive form of the protein suggested that mitochondrial cyt c in its reduced state modulates AA-PCD and this occurs independently on its function as an electron carrier.

Yeast cells have a single gene, YCA1, encoding a type I metacaspase that was first implicated in the execution of oxidative stress-induced PCD. AA-PCD can occur via two alternative pathways, one dependent and the other independent of YCA1. The two pathways differ one from another since the latter occurs without cyt c release, which requires YCA1, and is not sensitive to the antioxidant NAC (Figure 1). YCA1 participates in the AA-PCD in a manner unrelated to caspase-like activity increase which is the latest event of AA-PCD occurring at 200 min from death induction. YCA1 also exerts a non-death role contributing to clearance of insoluble protein aggregates over the natural yeast lifespan promoting its longevity and fitness.

Interestingly enough, Gup1p, an O-acyltransferase required for several cellular processes including lipid metabolism and membrane remodeling, is required for AA-PCD to occur with δgup1 cells dying by necrosis in response to acetic acid or in chronological aging.

THE MITOCHONDRIAL RETROGRADE PATHWAY IN YEAST CYTOPROTECTION

Acetic acid stress sensitivity of yeast cells strongly depends on the extracellular environment. Indeed, when AA-PCD is induced in yeast cells growing on glucose as carbon source at pH 3.0, it has been shown that 30 min pre-conditioning in pH 3.0 medium set by HCl prior to acetic acid administration protects S. cerevisiae cells from AA-PCD. Since acetic acid is absent in the pre-conditioning medium, the hypothesis that the Hog1p-dependent degradation of Fps1p, described in Section “Acetic Acid Stress and Yeast Adaptation,” could be involved in acid pre-conditioning should be ruled out.

Instead, differently from AA-PCD cells, in acid stress-adapted cells acetic acid treatment does not cause any increase in intracellular ROS production. Since mitochondria are the main source of ROS and a decline of mitochondrial function is observed en route to AA-PCD, activation of mitochondrial stress response might be hypothesized under acid stress adaptation. Figure 1 shows certain signaling pathways involved in cell response to mitochondrial dysfunction that may have a role in the cross-talk between cell death and adaptation mechanisms activated by acetic acid stress in yeast. The best characterized mechanism of cell response to mitochondrial dysfunction is the retrograde (RTG) pathway. Components and molecular details of RTG pathway have been better characterized in yeast. RTG-target gene expression is largely increased in cells with compromised mitochondrial function, such as cells lacking mitochondrial DNA (ρ0; ). Rtg1p and Rtg3p are transcription factors that interact as a heterodimer to bind target sites called R boxes (GTCAC) located in the promoter region of the RTG target genes. Activation of Rtg3p correlates with its partial de-phosphorylation and its translocation with Rtg1p from the cytoplasm to the nucleus. Rtg2p acts upstream of the Rtg1/Rtg3p complex, being both a proximal sensor of the mitochondrial dysfunction and a transducer of mitochondrial signals controlling Rtg1/3p nuclear localization through the reversible binding with Mks1p, a negative regulator of the RTG pathway. Other positive and negative regulators of the RTG pathway include Bmh1p, Bmh2p, Grr1p, and Lst8p. Hog1p has been shown to control Rtg1/3p nuclear localization and to phosphorylate Rtg3p upon osmostress. Activation of the RTG pathway leads to up-regulation of a subset of nuclear genes whose products function in anaplerotic pathways, fatty acid oxidation, and glyoxylate cycle.

It is of note that the RTG pathway is linked to other signaling pathways, such as target of rapamycin (TOR) pathway, which regulates cell growth in response to nutrient availability, and it has been reported to inhibit Rtg1/3-dependent gene expression. However, it is clear that these two pathways do not overlap but act in parallel to converge on Rtg1/3p. The RTG response is also related to the Ras–cAMP signaling pathway. The inappropriate activation of PKA can lead to the production of dysfunctional, ROS generating mitochondria, and apoptosis (;;; Figure 1). In this context, it is of note that both TOR and Ras–cAMP–PKA signaling pathways are causally involved in yeast AA-PCD.

Our initial results suggest that RTG-dependent signaling may be activated in response to mitochondrial dysfunction in acid-stressed S. cerevisiae cells grown in the low pH medium used for cell pre-conditioning. In this conditions, the gene encoding peroxisomal citrate synthase (CIT2), is up-regulated in ρ0 cells compared to respiratory competent ρ+ cells, a hallmark of RTG-dependent transcription activation. On the contrary, RTG pathway remains inactive in response to mitochondrial dysfunction in cells grown in neutral pH medium, which are sensitive to AA-PCD induction (unpublished results). This points to a possible role of RTG pathway in AA-PCD signaling.

Mitochondrial RTG signaling occurs also in mammalian cells as a result of mtDNA mutation/deletion, oxidative stress, hypoxia, treatments with specific inhibitors of the respiratory chain or drugs. The signaling cascade is characterized by the activation of different nuclear transcription factors, including NF-κB which controls the transcription of a variety of target genes involved in the general stress response. In terms of pro-survival and adaptive response, the RTG-dependent signaling pathway in yeast and the NF-κB pathway active in mammalian cells appear to be involved in a conserved mechanism of cell stress response, validating yeast as a model to study mitochondrial stress response pathways.

Even a traditional industry such as wine production is taking over the challenge of tailoring genetically customized wine-yeast strains. Market-oriented wine-yeast strains are currently being developed for the cost-competitive production of wine with minimized resource inputs, improved quality, and low environmental impact. The comprehension of the complex mechanism integrating the signaling network activated by acetic acid per se, nutrient availability and metabolic conditions will greatly impact the improvement of both biological control of wine-spoilage microorganisms and, on the other hand, wine-yeast fermentation performances. With this respect, it is of note that laboratory yeast strains are unable to completely transform all the sugar in the grape must into ethanol under winemaking conditions, where multiple stresses occur simultaneously and sequentially throughout the fermentation. Post-genomic techniques and a systems biology approach will help to elucidate how the responses of wine yeasts to these stimuli differs from laboratory strains.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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    Madeo F. Herker E. Maldener C. Wissing S. Lachelt S. Herlan M. (2002 ). A caspase-related protease regulates apoptosis in yeast. Mol. Cell 9 911–917

    Not in our library10.1016/s1097-2765(02)00501-4

  53. 53.

    Martinez-Munoz G. A. Kane P. (2008 ). Vacuolar and plasma membrane proton pumps collaborate to achieve cytosolic pH homeostasis in yeast. J. Biol. Chem. 283 20309–20319

    Not in our library10.1074/jbc.m710470200

  54. 54.

    Mira N. P. Becker J. D. Sa-Correia I. (2010a ). Genomic expression program involving the Haa1p-regulon in Saccharomyces cerevisiae response to acetic acid. OMICS 14 587–601

    Not in our library10.1089/omi.2010.0048

  55. 55.
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    No notice
  56. 56.

    Mira N. P. Teixeira M. C. Sa-Correia I. (2010c ). Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae: a genome-wide view. OMICS 14 525–540

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    Mira N. P. Henriques S. F. Keller G. Teixeira M. C. Matos R. G. Arraiano C. M. (2011 ). Identification of a DNA-binding site for the transcription factor Haa1, required for Saccharomyces cerevisiae response to acetic acid stress. Nucleic Acids Res. 39 6896–6907

    Not in our library10.1093/nar/gkr228

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    Mitchell A. Romano G. H. Groisman B. Yona A. Dekel E. Kupiec M. (2009 ). Adaptive prediction of environmental changes by microorganisms. Nature 460 220–224

    Not in our library10.1038/nature08112

  59. 59.

    Mollapour M. Piper P. W. (2006 ). Hog1p mitogen-activated protein kinase determines acetic acid resistance in Saccharomyces cerevisiae. FEMS Yeast Res. 6 1274–1280

    Not in our library10.1111/j.1567-1364.2006.00118.x

  60. 60.

    Mollapour M. Piper P. W. (2007 ). Hog1 mitogen-activated protein kinase phosphorylation targets the yeast Fps1 aquaglyceroporin for endocytosis, thereby rendering cells resistant to acetic acid. Mol. Cell. Biol. 27 6446–6456

    Not in our library10.1128/mcb.02205-06

  61. 61.

    Mollapour M. Shepherd A. Piper P. W. (2008 ). Novel stress responses facilitate Saccharomyces cerevisiae growth in the presence of the monocarboxylate preservatives. Yeast 25 169–177

    Not in our library10.1002/yea.1576

  62. 62.

    Mollapour M. Shepherd A. Piper P. W. (2009 ). Presence of the Fps1p aquaglyceroporin channel is essential for Hog1p activation, but suppresses Slt2(Mpk1)p activation, with acetic acid stress of yeast. Microbiology 155 3304–3311

    Not in our library10.1099/mic.0.030502-0

  63. 63.

    Mroczek S. Kufel J. (2008 ). Apoptotic signals induce specific degradation of ribosomal RNA in yeast. Nucleic Acids Res. 36 2874–2888

    Not in our library10.1093/nar/gkm1100

  64. 64.
    Gis1 and Rph1 regulate glycerol and acetate metabolism in glucose depleted yeast cells. · 2012
    Not checked
  65. 65.

    Paiva S. Devaux F. Barbosa S. Jacq C. Casal M. (2004 ). Ady2p is essential for the acetate permease activity in the yeast Saccharomyces cerevisiae. Yeast 21 201–210

    Not in our library10.1002/yea.1056

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    Pereira C. Camougrand N. Manon S. Sousa M. J. Corte-Real M. (2007 ). ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosis. Mol. Microbiol. 66 571–582

    Not in our library10.1111/j.1365-2958.2007.05926.x

  67. 67.

    Pereira C. Silva R. D. Saraiva L. Johansson B. Sousa M. J. Corte-Real M. (2008 ). Mitochondria-dependent apoptosis in yeast. Biochim. Biophys. Acta 1783 1286–1302

    Not in our library10.1016/j.bbamcr.2008.03.010

  68. 68.

    Phillips A. J. Crowe J. D. Ramsdale M. (2006 ). Ras pathway signaling accelerates programmed cell death in the pathogenic fungus Candida albicans. Proc. Natl. Acad. Sci. U.S.A. 103 726–731

    Not in our library10.1073/pnas.0506405103

  69. 69.

    Pinto I. Cardoso H. Leao C Van Uden N. (1989 ). High enthalpy and low enthalpy death in Saccharomyces cerevisiae induced by acetic acid. Biotechnol. Bioeng. 33 1350–1352

    Not in our library10.1002/bit.260331019

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    Piper P. Calderon C. O. Hatzixanthis K. Mollapour M. (2001 ). Weak acid adaptation: the stress response that confers yeasts with resistance to organic acid food preservatives. Microbiology 147 2635–2642

    Not in our library10.1099/00221287-147-10-2635

  71. 71.

    Piper P. W. (1999 ). Yeast superoxide dismutase mutants reveal a pro-oxidant action of weak organic acid food preservatives. Free Radic. Biol. Med. 27 1219–1227

    Not in our library10.1016/s0891-5849(99)00147-1

  72. 72.

    Piper P. W. (2011 ). “Resistance of yeasts to wek organic acid food preservatives,” in Advances in Applied Microbiology, edsLaskin A. Gadd G. Sariaslani S. (Burlington: Academic Press) 97–113

    Not in our library10.1016/b978-0-12-387044-5.00004-2

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    Pizarro F. Vargas F. A. Agosin E. (2007 ). A systems biology perspective of wine fermentations. Yeast 24 977–991

    Not in our library10.1002/yea.1545

  74. 74.

    Pretorius I. S. (2000 ). Tailoring wine yeast for the new millennium: novel approaches to the ancient art of winemaking. Yeast 16 675–729

    Not in our library10.1002/1097-0061(20000615)16:8<675::aid-yea585>3.0.co;2-b

  75. 75.

    Pretorius I. S. Bauer F. F. (2002 ). Meeting the consumer challenge through genetically customized wine-yeast strains. Trends Biotechnol. 20 426–432

    Not in our library10.1016/s0167-7799(02)02049-8

  76. 76.

    Ribeiro G. F. Corte-Real M. Johansson B. (2006 ). Characterization of DNA damage in yeast apoptosis induced by hydrogen peroxide, acetic acid, and hyperosmotic shock. Mol. Biol. Cell 17 4584–4591

    Not in our library10.1091/mbc.e06-05-0475

  77. 77.

    Rodrigues F. Sousa M. J. Ludovico P. Santos H. Corte-Real M. Leao C. (2012 ). The fate of acetic acid during glucose Co-metabolism by the spoilage yeast Zygosaccharomyces bailii. PLoS ONE 7:e52402

    Not in our library10.1371/journal.pone.0052402

  78. 78.

    Rolland F. Winderickx J. Thevelein J. M. (2002 ). Glucose-sensing and -signalling mechanisms in yeast. FEMS Yeast Res. 2 183–201

    Not in our library10.1111/j.1567-1364.2002.tb00084.x

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    Ruiz-Roig C. Noriega N. Duch A. Posas F De Nadal E. (2012 ). The Hog1 SAPK controls the Rtg1/Rtg3 transcriptional complex activity by multiple regulatory mechanisms. Mol. Biol. Cell 23 4286–4296

    Not in our library10.1091/mbc.e12-04-0289

  80. 80.

    Schuller C. Mamnun Y. M. Mollapour M. Krapf G. Schuster M. Bauer B. E. (2004 ). Global phenotypic analysis and transcriptional profiling defines the weak acid stress response regulon in Saccharomyces cerevisiae. Mol. Biol. Cell 15 706–720

    Not in our library10.1091/mbc.e03-05-0322

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    Mitochondria-to-Nuclear Signaling Is Regulated by the Subcellular Localization of the Transcription Factors Rtg1p and Rtg3p · 2000
    Not checked
  82. 82.

    Sousa M. J. Rodrigues F. Corte-Real M. Leao C. (1998 ). Mechanisms underlying the transport and intracellular metabolism of acetic acid in the presence of glucose in the yeast Zygosaccharomyces bailii. Microbiology 144(Pt 3) 665–670

    Not in our library10.1099/00221287-144-3-665

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    Srinivasan V. Kriete A. Sacan A. Jazwinski S. M. (2010 ). Comparing the yeast retrograde response and NF-kappaB stress responses: implications for aging. Aging Cell 9 933–941

    Not in our library10.1111/j.1474-9726.2010.00622.x

  84. 84.

    Stratford M. (2006 ). “Food and beverage spoilage yeasts.,” in Yeasts in Food and Beverages, ed. Querol A. Fleet G. (Berlin: Springer) 335–379

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    Stratford M. Anslow P. A. (1996 ). Comparison of the inhibitory action on Saccharomyces cerevisiae of weak-acid preservatives, uncouplers, and medium-chain fatty acids. FEMS Microbiol. Lett. 142 53–58

    Not in our library10.1111/j.1574-6968.1996.tb08407.x

  86. 86.

    Stratford M. Anslow P. A. (1998 ). Evidence that sorbic acid does not inhibit yeast as a classic ‘weak acid preservative’. Lett. Appl. Microbiol. 27 203–206

    Not in our library10.1046/j.1472-765x.1998.00424.x

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    Tulha J. Faria-Oliveira F. Lucas C. Ferreira C. (2012 ). Programmed cell death in Saccharomyces cerevisiae is hampered by the deletion of GUP1 gene. BMC Microbiol. 12:80

    Not in our library10.1186/1471-2180-12-80

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    Ullah A. Orij R. Brul S. Smits G. J. (2012 ). Quantitative analysis of the modes of growth inhibition by weak organic acids in yeast. Appl. Environ. Microbiol. 78 8377–8387

    Not in our library10.1128/aem.02126-12

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    Uren A. G. O’rourke K. Aravind L. A. Pisabarro M. T. Seshagiri S. Koonin E. V. (2000 ). Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol. Cell 6 961–967

    Not in our library10.1016/s1097-2765(00)00094-0

  90. 90.

    Vilela-Moura A. Schuller D. Mendes-Faia A. Corte-Real M. (2008 ). Reduction of volatile acidity of wines by selected yeast strains. Appl. Microbiol. Biotechnol. 80 881–890

    Not in our library10.1007/s00253-008-1616-x

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    Vilela-Moura A. Schuller D. Mendes-Faia A. Silva R. D. Chaves S. R. Sousa M. J. (2010 ). The impact of acetate metabolism on yeast fermentative performance and wine quality: reduction of volatile acidity of grape musts and wines. Appl. Microbiol. Biotechnol. 89 271–280

    Not in our library10.1007/s00253-010-2898-3

  92. 92.

    Weinberger M. Mesquita A. Caroll T. Marks L. Yang H. Zhang Z. (2010 ). Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence. Aging (Albany NY) 2 709–726

    Not in our library10.18632/aging.100215

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    Wilkinson D. Ramsdale M. (2011 ). Proteases and caspase-like activity in the yeast Saccharomyces cerevisiae. Biochem. Soc. Trans. 39 1502–1508

    Not in our library10.1042/bst0391502

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    Ždralević M. Guaragnella N. Antonacci L. Marra E. Giannattasio S. (2012 ). Yeast as a tool to study signaling pathways in mitochondrial stress response and cytoprotection. ScientificWorldJournal 2012 912147

    Not in our library10.1100/2012/912147

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    Zhang J. G. Liu X. Y. He X. P. Guo X. N. Lu Y. Zhang B. R. (2011 ). Improvement of acetic acid tolerance and fermentation performance of Saccharomyces cerevisiae by disruption of the FPS1 aquaglyceroporin gene. Biotechnol. Lett. 33 277–284

    Not in our library10.1007/s10529-010-0433-3

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