scholarly journals Bulk autophagy induction and life extension is achieved when iron is the only limited nutrient in Saccharomyces cerevisiae

2021 ◽  
Vol 478 (4) ◽  
pp. 811-837
Author(s):  
Sandra Montella-Manuel ◽  
Nuria Pujol-Carrion ◽  
Mónica A. Mechoud ◽  
Maria Angeles de la Torre-Ruiz
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Stress Resistance ◽  
Primary Response ◽  
Iron Limitation ◽  
Life Extension ◽  
Quiescent State ◽  
Autophagy Flux ◽  
Iron Deprivation ◽  
Autophagy Induction ◽  
Subsequent Activity

We have investigated the effects that iron limitation provokes in Saccharomyces cerevisiae exponential cultures. We have demonstrated that one primary response is the induction of bulk autophagy mediated by TORC1. Coherently, Atg13 became dephosphorylated whereas Atg1 appeared phosphorylated. The signal of iron deprivation requires Tor2/Ypk1 activity and the inactivation of Tor1 leading to Atg13 dephosphorylation, thus triggering the autophagy process. Iron replenishment in its turn, reduces autophagy flux through the AMPK Snf1 and the subsequent activity of the iron-responsive transcription factor, Aft1. This signalling converges in Atg13 phosphorylation mediated by Tor1. Iron limitation promotes accumulation of trehalose and the increase in stress resistance leading to a quiescent state in cells. All these effects contribute to the extension of the chronological life, in a manner totally dependent on autophagy activation.

scholarly journals VTC4 Polyphosphate Polymerase Knockout Increases Stress Resistance of Saccharomyces cerevisiae Cells

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 487
Author(s):  
Alexander Tomashevsky ◽  
Ekaterina Kulakovskaya ◽  
Ludmila Trilisenko ◽  
Ivan V. Kulakovskiy ◽  
Tatiana Kulakovskaya ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Heavy Metal ◽  
Stress Response ◽  
Stress Resistance ◽  
Alkaline Stress ◽  
Inorganic Polyphosphate ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Elevated Expression ◽  
Chaperone Complex

Inorganic polyphosphate (polyP) is an important factor of alkaline, heavy metal, and oxidative stress resistance in microbial cells. In yeast, polyP is synthesized by Vtc4, a subunit of the vacuole transporter chaperone complex. Here, we report reduced but reliably detectable amounts of acid-soluble and acid-insoluble polyPs in the Δvtc4 strain of Saccharomyces cerevisiae, reaching 10% and 20% of the respective levels of the wild-type strain. The Δvtc4 strain has decreased resistance to alkaline stress but, unexpectedly, increased resistance to oxidation and heavy metal excess. We suggest that increased resistance is achieved through elevated expression of DDR2, which is implicated in stress response, and reduced expression of PHO84 encoding a phosphate and divalent metal transporter. The decreased Mg2+-dependent phosphate accumulation in Δvtc4 cells is consistent with reduced expression of PHO84. We discuss a possible role that polyP level plays in cellular signaling of stress response mobilization in yeast.

scholarly journals The Fish Pathogen Vibrio ordalii Under Iron Deprivation Produces the Siderophore Piscibactin

2019 ◽  
Vol 7 (9) ◽  
pp. 313 ◽  
Author(s):  
Pamela Ruiz ◽  
Miguel Balado ◽  
Juan Carlos Fuentes-Monteverde ◽  
Alicia E. Toranzo ◽  
Jaime Rodríguez ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Iron Uptake ◽  
Peptide Mass Fingerprinting ◽  
Iron Limitation ◽  
Fish Pathogen ◽  
Fish Pathogens ◽  
Iron Deprivation ◽  
Peptide Mass ◽  
Photobacterium Damselae ◽  
Vibrio Ordalii

Vibrio ordalii is the causative agent of vibriosis, mainly in salmonid fishes, and its virulence mechanisms are still not completely understood. In previous works we demonstrated that V. ordalii possess several iron uptake mechanisms based on heme utilization and siderophore production. The aim of the present work was to confirm the production and utilization of piscibactin as a siderophore by V. ordalii. Using genetic analysis, identification by peptide mass fingerprinting (PMF) of iron-regulated membrane proteins and chemical identification by LC-HRMS, we were able to clearly demonstrate that V. ordalii produces piscibactin under iron limitation. The synthesis and transport of this siderophore is encoded by a chromosomal gene cluster homologous to another one described in V. anguillarum, which also encodes the synthesis of piscibactin. Using β-galactosidase assays we were able to show that two potential promoters regulated by iron control the transcription of this gene cluster in V. ordalii. Moreover, biosynthetic and transport proteins corresponding to piscibactin synthesis and uptake could be identified in membrane fractions of V. ordalii cells grown under iron limitation. The synthesis of piscibactin was previously reported in other fish pathogens like Photobacterium damselae subsp. piscicida and V. anguillarum, which highlights the importance of this siderophore as a key virulence factor in Vibrionaceae bacteria infecting poikilothermic animals.

Cellular Differentiation in Response to Nutrient Availability: The Repressor of Meiosis, Rme1p, Positively Regulates Invasive Growth in Saccharomyces cerevisiae

Genetics ◽  
2003 ◽  
Vol 165 (3) ◽  
pp. 1045-1058
Author(s):  
Dewald van Dyk ◽  
Guy Hansson ◽  
Isak S Pretorius ◽  
Florian F Bauer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cellular Differentiation ◽  
Promoter Sequence ◽  
Quiescent State ◽  
Invasive Growth ◽  
Limited Growth ◽  
Yeast Saccharomyces Cerevisiae ◽  
A Cell ◽  
Signaling Modules ◽  
Differentiation Pathways

Abstract In the yeast Saccharomyces cerevisiae, the transition from a nutrient-rich to a nutrient-limited growth medium typically leads to the implementation of a cellular adaptation program that results in invasive growth and/or the formation of pseudohyphae. Complete depletion of essential nutrients, on the other hand, leads either to entry into a nonbudding, metabolically quiescent state referred to as G0 in haploid strains or to meiosis and sporulation in diploids. Entry into meiosis is repressed by the transcriptional regulator Rme1p, a zinc-finger-containing DNA-binding protein. In this article, we show that Rme1p positively regulates invasive growth and starch metabolism in both haploid and diploid strains by directly modifying the transcription of the FLO11 (also known as MUC1) and STA2 genes, which encode a cell wall-associated protein essential for invasive growth and a starch-degrading glucoamylase, respectively. Genetic evidence suggests that Rme1p functions independently of identified signaling modules that regulate invasive growth and of other transcription factors that regulate FLO11 and that the activation of FLO11 is dependent on the presence of a promoter sequence that shows significant homology to identified Rme1p response elements (RREs). The data suggest that Rme1p functions as a central switch between different cellular differentiation pathways.

GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats

1991 ◽  
Vol 11 (10) ◽  
pp. 5101-5112
Author(s):  
J S Flick ◽  
M Johnston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Interactions ◽  
Tandem Repeats ◽  
Glucose Repression ◽  
Molecular Data ◽  
Primary Response ◽  
Yeast Cells ◽  
Cell Fractionation ◽  
Protein Protein Interactions ◽  
Yeast Saccharomyces Cerevisiae

Growth of the yeast Saccharomyces cerevisiae on glucose leads to repression of transcription of many genes required for alternative carbohydrate metabolism. The GRR1 gene appears to be of central importance to the glucose repression mechanism, because mutations in GRR1 result in a pleiotropic loss of glucose repression (R. Bailey and A. Woodword, Mol. Gen. Genet. 193:507-512, 1984). We have isolated the GRR1 gene and determined that null mutants are viable and display a number of growth defects in addition to the loss of glucose repression. Surprisingly, grr1 mutations convert SUC2, normally a glucose-repressed gene, into a glucose-induced gene. GRR1 encodes a protein of 1,151 amino acids that is expressed constitutively at low levels in yeast cells. GRR1 protein contains 12 tandem repeats of a sequence similar to leucine-rich motifs found in other proteins that may mediate protein-protein interactions. Indeed, cell fractionation studies are consistent with this view, suggesting that GRR1 protein is tightly associated with a particulate protein fraction in yeast extracts. The combined genetic and molecular data are consistent with the idea that GRR1 protein is a primary response element in the glucose repression pathway and is required for the generation or interpretation of the signal that induces glucose repression.

scholarly journals Interactions of GMP with Human Glrx3 and with Saccharomyces cerevisiae Grx3 and Grx4 Converge in the Regulation of the Gcn2 Pathway

2020 ◽  
Vol 86 (14) ◽  
Author(s):  
Mónica A. Mechoud ◽  
Nuria Pujol-Carrion ◽  
Sandra Montella-Manuel ◽  
Maria Angeles de la Torre-Ruiz
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Heterologous Expression ◽  
Mammalian Cells ◽  
Iron Homeostasis ◽  
Life Extension ◽  
Iron Sulfur Clusters ◽  
Content Type ◽  
Functional Conservation ◽  
Iron Sulfur ◽  
Cell Life

ABSTRACT The human monothiol glutaredoxin Glrx3 (PICOT) is ubiquitously distributed in cytoplasm and nuclei in mammalian cells. Its overexpression has been associated with the development of several types of tumors, whereas its deficiency might cause retardation in embryogenesis. Its exact biological role has not been well resolved, although a function as a chaperone distributing iron/sulfur clusters is currently accepted. Yeast humanization and the use of a mouse library have allowed us to find a new partner for PICOT: the human GMP synthase (hGMPs). Both proteins carry out collaborative functions regarding the downregulation of the Saccharomyces cerevisiae Gcn2 pathway under conditions of nutritional stress. Glrx3/hGMPs interact through conserved residues that bridge iron/sulfur clusters and glutathione. This mechanism is also conserved in budding yeast, whose proteins Grx3/Grx4, along with GUA1 (S. cerevisiae GMPs), also downregulate the integrated stress response (ISR) pathway. The heterologous expression of Glrx3/hGMPs efficiently complements Grx3/Grx4. Moreover, the heterologous expression of Glrx3 efficiently complements the novel participation in chronological life span that has been characterized for both Grx3 and Grx4. Our results underscore that the Glrx3/Grx3/Grx4 family presents an evolutionary and functional conservation in signaling events that is partly related to GMP function and contributes to cell life extension. IMPORTANCE Saccharomyces cerevisiae is an optimal eukaryotic microbial model to study biological processes in higher organisms despite the divergence in evolution. The molecular function of yeast glutaredoxins Grx3 and Grx4 is enormously interesting, since both proteins are required to maintain correct iron homeostasis and an efficient response to oxidative stress. The human orthologous Glrx3 (PICOT) is involved in a number of human diseases, including cancer. Our research expanded its utility to human cells. Yeast has allowed the characterization of GMP synthase as a new interacting partner for Glrx3 and also for yeast Grx3 and Grx4, the complex monothiol glutaredoxins/GMPs that participate in the downregulation of the activity of the Gcn2 stress pathway. This mechanism is conserved in yeast and humans. Here, we also show that this family of glutaredoxins, Grx3/Grx4/Glrx3, also has a function related to life extension.

scholarly journals The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

2004 ◽  
Vol 48 (6) ◽  
pp. 1983-1988 ◽  
Author(s):  
Michael V. Bland ◽  
Salim Ismail ◽  
Jack A. Heinemann ◽  
Jacqueline I. Keenan
Keyword(s):  
Helicobacter Pylori ◽  
Antimicrobial Effect ◽  
Iron Limitation ◽  
Intracellular Iron ◽  
Colloidal Bismuth Subcitrate ◽  
Iron Deprivation ◽  
Atp Levels ◽  
Bismuth Subcitrate ◽  
Membrane Changes ◽  
H Pylori

ABSTRACT Helicobacter pylori is highly susceptible to bismuth, a heavy metal with antimicrobial activity linked to its effect on bacterial iron uptake. Three strains of H. pylori were analyzed for indicators of iron limitation following exposure to the MIC of colloidal bismuth subcitrate (MICCBS). Similar morphologic and outer membrane changes were observed following growth in iron-limiting medium and at the MICCBS that inhibited the growth of all three strains. These changes, which were also observed for iron-limited bacteria, were alleviated by the addition of iron to the cultures. H. pylori ATP levels, reduced in iron-limiting medium, were below the limits of detection in two of the three strains following exposure to bismuth. The addition of iron partially restored bacterial ATP levels in these two strains, although not to normal concentrations. In contrast, exposure of the same strains to the MICCBS failed to deplete intracellular levels of iron, which were significantly reduced by culturing in iron-limiting medium. Thus, the antimicrobial effect of bismuth and of iron limitation on H. pylori may be similar. However, the respective mechanisms of intracellular action would appear to be mediated by different pathways within the cell.

Heterogeneity of stress gene expression and stress resistance among individual cells of Saccharomyces cerevisiae

2001 ◽  
Vol 40 (4) ◽  
pp. 1000-1008 ◽  
Author(s):  
Paul V. Attfield ◽  
Hung Yoon Choi ◽  
Duncan A. Veal ◽  
Philip J. L. Bell
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Stress Resistance ◽  
Stress Gene

RTG1- and RTG2-dependent retrograde signaling controls mitochondrial activity and stress resistance in Saccharomyces cerevisiae

2015 ◽  
Vol 81 ◽  
pp. 30-37 ◽  
Author(s):  
Nicole Quesada Torelli ◽  
José Ribamar Ferreira-Júnior ◽  
Alicia J. Kowaltowski ◽  
Fernanda Marques da Cunha
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Stress Resistance ◽  
Retrograde Signaling ◽  
Mitochondrial Activity

scholarly journals Chlamydial Hsp60-2 Is Iron Responsive in Chlamydia trachomatis Serovar E-Infected Human Endometrial Epithelial Cells In Vitro

2007 ◽  
Vol 75 (5) ◽  
pp. 2374-2380 ◽  
Author(s):  
Richard W. LaRue ◽  
Brian D. Dill ◽  
David K. Giles ◽  
Judy D. Whittimore ◽  
Jane E. Raulston
Keyword(s):  
Chlamydia Trachomatis ◽  
Growth Conditions ◽  
Iron Limitation ◽  
Iron Deprivation ◽  
Iron Deficient ◽  
Deficient Medium ◽  
Enhanced Expression ◽  
Shock Proteins ◽  
Endometrial Epithelial Cells

ABSTRACT Chlamydial 60-kDa heat shock proteins (cHsp60s) are known to play a prominent role in the immunopathogenesis of disease. It is also known that several stress-inducing growth conditions, such as heat, iron deprivation, or exposure to gamma interferon, result in the development of persistent chlamydial forms that often exhibit enhanced expression of cHsp60. We have shown previously that the expression of cHsp60 is greatly enhanced in Chlamydia trachomatis serovar E propagated in an iron-deficient medium. The objective of this work was to determine which single cHsp60 or combination of the three cHsp60 homologs encoded by this organism responds to iron limitation. Using monospecific polyclonal peptide antisera that recognize only cHsp60-1, cHsp60-2, or cHsp60-3, we found that expression of cHsp60-2 is responsive to iron deprivation. Overall, our studies suggest that the expression of cHsp60 homologs differs among the mechanisms currently known to induce persistence.

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