scholarly journals High Osmolarity Extends Life Span in Saccharomyces cerevisiae by a Mechanism Related to Calorie Restriction

2002 ◽  
Vol 22 (22) ◽  
pp. 8056-8066 ◽  
Author(s):  
Matt Kaeberlein ◽  
Alex A. Andalis ◽  
Gerald R. Fink ◽  
Leonard Guarente

ABSTRACT Calorie restriction (CR) extends life span in many different organisms, including mammals. We describe here a novel pathway that extends the life span of Saccharomyces cerevisiae mother cells but does not involve a reduction in caloric content of the media, i.e., there is growth of yeast cells in the presence of a high concentration of external osmolytes. Like CR, this longevity-promoting response to high osmolarity requires SIR2, suggesting a common mechanism of life span regulation. Genetic and microarray analysis indicates that high osmolarity extends the life span by activating Hog1p, leading to an increase in the biosynthesis of glycerol from glycolytic intermediates. This metabolic shift likely increases NAD levels, thereby activating Sir2p and promoting longevity.

1994 ◽  
Vol 127 (6) ◽  
pp. 1985-1993 ◽  
Author(s):  
B K Kennedy ◽  
N R Austriaco ◽  
L Guarente

The yeast Saccharomyces cerevisiae typically divides asymmetrically to give a large mother cell and a smaller daughter cell. As mother cells become old, they enlarge and produce daughter cells that are larger than daughters derived from young mother cells. We found that occasional daughter cells were indistinguishable in size from their mothers, giving rise to a symmetric division. The frequency of symmetric divisions became greater as mother cells aged and reached a maximum occurrence of 30% in mothers undergoing their last cell division. Symmetric divisions occurred similarly in rad9 and ste12 mutants. Strikingly, daughters from old mothers, whether they arose from symmetric divisions or not, displayed reduced life spans relative to daughters from young mothers. Because daughters from old mothers were larger than daughters from young mothers, we investigated whether an increased size per se shortened life span and found that it did not. These findings are consistent with a model for aging that invokes a senescence substance which accumulates in old mother cells and is inherited by their daughters.


1994 ◽  
Vol 14 (6) ◽  
pp. 4135-4144
Author(s):  
J Albertyn ◽  
S Hohmann ◽  
J M Thevelein ◽  
B A Prior

The yeast Saccharomyces cerevisiae responds to osmotic stress, i.e., an increase in osmolarity of the growth medium, by enhanced production and intracellular accumulation of glycerol as a compatible solute. We have cloned a gene encoding the key enzyme of glycerol synthesis, the NADH-dependent cytosolic glycerol-3-phosphate dehydrogenase, and we named it GPD1. gpd1 delta mutants produced very little glycerol, and they were sensitive to osmotic stress. Thus, glycerol production is indeed essential for the growth of yeast cells during reduced water availability. hog1 delta mutants lacking a protein kinase involved in osmostress-induced signal transduction (the high-osmolarity glycerol response [HOG] pathway) failed to increase glycerol-3-phosphate dehydrogenase activity and mRNA levels when osmotic stress was imposed. Thus, expression of GPD1 is regulated through the HOG pathway. However, there may be Hog1-independent mechanisms mediating osmostress-induced glycerol accumulation, since a hog1 delta strain could still enhance its glycerol content, although less than the wild type. hog1 delta mutants are more sensitive to osmotic stress than isogenic gpd1 delta strains, and gpd1 delta hog1 delta double mutants are even more sensitive than either single mutant. Thus, the HOG pathway most probably has additional targets in the mechanism of adaptation to hypertonic medium.


2020 ◽  
Vol 48 (19) ◽  
pp. 10877-10889 ◽  
Author(s):  
Yaxin Yu ◽  
Robert M Yarrington ◽  
David J Stillman

Abstract The Saccharomyces cerevisiae HO gene is a model regulatory system with complex transcriptional regulation. Budding yeast divide asymmetrically and HO is expressed only in mother cells where a nucleosome eviction cascade along the promoter during the cell cycle enables activation. HO expression in daughter cells is inhibited by high concentration of Ash1 in daughters. To understand how Ash1 represses transcription, we used a myo4 mutation which boosts Ash1 accumulation in both mothers and daughters and show that Ash1 inhibits promoter recruitment of SWI/SNF and Gcn5. We show Ash1 is also required for the efficient nucleosome repopulation that occurs after eviction, and the strongest effects of Ash1 are seen when Ash1 has been degraded and at promoter locations distant from where Ash1 bound. Additionally, we defined a specific nucleosome/nucleosome-depleted region structure that restricts HO activation to one of two paralogous DNA-binding factors. We also show that nucleosome eviction occurs bidirectionally over a large distance. Significantly, eviction of the more distant nucleosomes is dependent upon the FACT histone chaperone, and FACT is recruited to these regions when eviction is beginning. These last observations, along with ChIP experiments involving the SBF factor, suggest a long-distance loop transiently forms at the HO promoter.


2019 ◽  
Author(s):  
Benjamin P Barré ◽  
Johan Hallin ◽  
Jia-Xing Yue ◽  
Karl Persson ◽  
Ekaterina Mikhalev ◽  
...  

ABSTRACTAging varies among individuals due to both genetics and environment but the underlying molecular mechanisms remain largely unknown. Using a highly recombinedSaccharomyces cerevisiaepopulation, we found 30 distinct Quantitative Trait Loci (QTLs) that control chronological life span (CLS) in calorie rich and calorie restricted environments, and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes, but through different genetic variants. We tracked the two major QTLs to massive expansions of intragenic tandem repeats in the cell wall glycoproteinsFLO11andHPF1, which caused a dramatic life span shortening. Life span impairment by N-terminalHPF1repeat expansion was partially buffered by rapamycin but not by calorie restriction. TheHPF1repeat expansion shifted yeast cells from a sedentary to a buoyant state, thereby increasing their exposure to surrounding oxygen. The higher oxygenation perturbed methionine, lipid, and purine metabolism, which likely explains the life span shortening. We conclude that fast evolving intragenic repeat expansions can fundamentally change the relationship between cells and their environment with profound effects on cellular life style and longevity.


2017 ◽  
Vol 474 (2) ◽  
pp. 301-315 ◽  
Author(s):  
Thales de P. Ribeiro ◽  
Fernanda L. Fonseca ◽  
Mariana D.C. de Carvalho ◽  
Rodrigo M. da C. Godinho ◽  
Fernando Pereira de Almeida ◽  
...  

Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2 and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.


1991 ◽  
Vol 114 (1) ◽  
pp. 111-123 ◽  
Author(s):  
J A Shaw ◽  
P C Mol ◽  
B Bowers ◽  
S J Silverman ◽  
M H Valdivieso ◽  
...  

The morphology of three Saccharomyces cerevisiae strains, all lacking chitin synthase 1 (Chs1) and two of them deficient in either Chs3 (calR1 mutation) or Chs2 was observed by light and electron microscopy. Cells deficient in Chs2 showed clumpy growth and aberrant shape and size. Their septa were very thick; the primary septum was absent. Staining with WGA-gold complexes revealed a diffuse distribution of chitin in the septum, whereas chitin was normally located at the neck between mother cell and bud and in the wall of mother cells. Strains deficient in Chs3 exhibited minor abnormalities in budding pattern and shape. Their septa were thin and trilaminar. Staining for chitin revealed a thin line of the polysaccharide along the primary septum; no chitin was present elsewhere in the wall. Therefore, Chs2 is specific for primary septum formation, whereas Chs3 is responsible for chitin in the ring at bud emergence and in the cell wall. Chs3 is also required for chitin synthesized in the presence of alpha-pheromone or deposited in the cell wall of cdc mutants at nonpermissive temperature, and for chitosan in spore walls. Genetic evidence indicated that a mutant lacking all three chitin synthases was inviable; this was confirmed by constructing a triple mutant rescued by a plasmid carrying a CHS2 gene under control of a GAL1 promoter. Transfer of the mutant from galactose to glucose resulted in cell division arrest followed by cell death. We conclude that some chitin synthesis is essential for viability of yeast cells.


1997 ◽  
Vol 17 (3) ◽  
pp. 1289-1297 ◽  
Author(s):  
S M Wurgler-Murphy ◽  
T Maeda ◽  
E A Witten ◽  
H Saito

In response to increases in extracellular osmolarity, Saccharomyces cerevisiae activates the HOG1 mitogen-activated protein kinase (MAPK) cascade, which is composed of a pair of redundant MAPK kinase kinases, namely, Ssk2p and Ssk22p, the MAPK kinase Pbs2p, and the MAPK Hog1p. Hog1p is activated by Pbs2p through phosphorylation of specific threonine and tyrosine residues. Activated Hog1p is essential for survival of yeast cells at high osmolarity. However, expression of constitutively active mutant kinases, such as those encoded by SSK2deltaN and PBS2(DD), is toxic and results in a lethal level of Hog1p activation. Overexpression of the protein tyrosine phosphatase Ptp2p suppresses the lethality of these mutations by dephosphorylating Hog1p. A catalytically inactive Cys-to-Ser Ptp2p mutant (Ptp2(C/S)p) is tightly bound to tyrosine-phosphorylated Hog1p in vivo. Disruption of PTP2 leads to elevated levels of tyrosine-phosphorylated Hog1p following exposure of cells to high osmolarity. Disruption of both PTP2 and another protein tyrosine phosphatase gene, PTP3, results in constitutive Hog1p tyrosine phosphorylation even in the absence of increased osmolarity. Thus, Ptp2p and Ptp3p are the major phosphatases responsible for the tyrosine dephosphorylation of Hog1p. When catalytically inactive Hog1(K/N)p is expressed in hog1delta cells, it is constitutively tyrosine phosphorylated. In contrast, Hog1(K/N)p, expressed together with wild-type Hog1p, is tyrosine phosphorylated only when cells are exposed to high osmolarity. Thus, the kinase activity of Hog1p is required for its own tyrosine dephosphorylation. Northern blot analyses suggest that Hog1p regulates Ptp2p and/or Ptp3p activity at the posttranscriptional level.


2016 ◽  
Vol 19 (0) ◽  
Author(s):  
Samuel Mariano-da-Silva ◽  
Rafael Dal Bosco Ducatti ◽  
Ivan Pedro Murari ◽  
Fabio Pilon

Summary The magnesium (Mg) capability to attenuate the toxicity of aluminum (Al) for the trehalose content, anaerobic growth, viability and budding rate of Saccharomyces cerevisiae, was studied in this work. Fermentations were carried out in triplicate with sterilized and diluted sugar cane media (4% total reducing sugars/pH 4.0) containing different Al (0.0, 50, 100 and 150 mg L-1) and Mg (0.0, 50 and 100 mg L-1) concentrations. The media were inoculated with 1 mL of 1% (wet basis) yeast suspension and incubated at 30ºC, 70 rpm for 20 hours in orbital shaker. At specific times during fermentation portions of cell suspension were taken out and the biomass concentration, yeast viability, budding rate and trehalose content on cells determined. The increase of Al levels, from 0.0 up to 150 mg L-1, showed a reduction on the yeast growth of approximately 95%, 55% and 18% as Mg increased from 0.0 to 50 and 100 mg L-1, respectively. The trehalose content experienced its lowest reduction when greater amounts of Mg were added to the fermentation process. Cell viability showed greater reductions as the content of Al in the media increased. Magnesium effectively protected yeast cells against the deleterious effects of Al on cell growth, viability, budding and trehalose content.


2021 ◽  
Vol 15 (3) ◽  
Author(s):  
S. Kovalchuk ◽  
T. Mudrak

Bioethanol production is a key issue that helps meet the growing demand for energy resources and ensure a sustainable economy. A promising direction is producing bioethanol by using the technology of fermentation of high-concentration wort obtained from the dry matter of grain raw materials. The purpose of this work is researching osmophilic races of distiller’s yeast under the conditions of fermentation of high-concentration wort at increased acidity. Selective breeding of a new strain of the yeast Saccharomyces cerevisiae DO-16 has allowed obtaining ethanol producers able to ferment grain wort with the dry matter concentration 24–34% at pH 6.0–3.0, with alcohol accumulation in the fermented wash up to 17% vol.  It has been studied how the pH of wort affects the dynamics of yeast cell synthesis by the distiller’s yeast races Saccharomyces cerevisiae DO-11 and Saccharomyces cerevisiae DO-16. It has been established that at the pH values 2.5, 3.0, 3.5, and 4.0, the concentration of yeast cells in the race Saccharomyces cerevisiae DO-16 was higher by 2.6, 1.7, 1.5, and 1.4 times respectively, as compared with Saccharomyces cerevisiae DO-11. It has been found that culturing industrial yeast of these races at low pH values ​​will provide not only the required sterility of the substrate, but also a high content of yeast cells, which is 250–320 million/cm³. The chemical and technological parameters of the fermented wash obtained by using the yeast races Saccharomyces cerevisiae DO-11 and DO-16 at the wort concentration 20–34% DM have been studied. It has been found that under all research conditions, the yeast of the race Saccharomyces cerevisiae DO-16 synthesised more ethanol than the strain Saccharomyces cerevisiae DO-11 did. The use of a new high-productive strain of Saccharomyces cerevisiae DO-16 will allow fermenting wort with a high ethanol concentration in the wash. It will also reduce the consumption of heat expended on isolating alcohol from the wash and of water expended on cooling, and lessen the amount of post-alcohol stillage.


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