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22 pages, 4857 KiB

Open AccessArticle

Human Sterols Are Overproduced, Stored and Excreted in Yeasts

by Astrid Radkohl, Veronika Schusterbauer, Lukas Bernauer, Gerald N. Rechberger, Heimo Wolinski, Matthias Schittmayer, Ruth Birner-Gruenberger, Gerhard G. Thallinger, Erich Leitner, Melanie Baeck, Harald Pichler and Anita Emmerstorfer-Augustin

Int. J. Mol. Sci. 2024, 25(2), 781; https://doi.org/10.3390/ijms25020781 - 8 Jan 2024

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Abstract

Sterols exert a profound influence on numerous cellular processes, playing a crucial role in both health and disease. However, comprehending the effects of sterol dysfunction on cellular physiology is challenging. Consequently, numerous processes affected by impaired sterol biosynthesis still elude our complete understanding. [...] Read more.

Sterols exert a profound influence on numerous cellular processes, playing a crucial role in both health and disease. However, comprehending the effects of sterol dysfunction on cellular physiology is challenging. Consequently, numerous processes affected by impaired sterol biosynthesis still elude our complete understanding. In this study, we made use of yeast strains that produce cholesterol instead of ergosterol and investigated the cellular response mechanisms on the transcriptome as well as the lipid level. The exchange of ergosterol for cholesterol caused the downregulation of phosphatidylethanolamine and phosphatidylserine and upregulation of phosphatidylinositol and phosphatidylcholine biosynthesis. Additionally, a shift towards polyunsaturated fatty acids was observed. While the sphingolipid levels dropped, the total amounts of sterols and triacylglycerol increased, which resulted in 1.7-fold enlarged lipid droplets in cholesterol-producing yeast cells. In addition to internal storage, cholesterol and its precursors were excreted into the culture supernatant, most likely by the action of ABC transporters Snq2, Pdr12 and Pdr15. Overall, our results demonstrate that, similarly to mammalian cells, the production of non-native sterols and sterol precursors causes lipotoxicity in K. phaffii, mainly due to upregulated sterol biosynthesis, and they highlight the different survival and stress response mechanisms on multiple, integrative levels. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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15 pages, 1491 KiB

Open AccessArticle

The Reaction of the Yeast Saccharomyces cerevisiae to Contamination of the Medium with Aflatoxins B₂ and G₁, Ochratoxin A and Zearalenone in Aerobic Cultures

by Grzegorz Kłosowski, Beata Koim-Puchowska, Joanna Dróżdż-Afelt and Dawid Mikulski

Int. J. Mol. Sci. 2023, 24(22), 16401; https://doi.org/10.3390/ijms242216401 - 16 Nov 2023

Cited by 1 | Viewed by 890

Abstract

The mechanisms by which yeast cells respond to environmental stress include the production of heat shock proteins (HSPs) and the reduction of oxidative stress. The response of yeast exposed to aflatoxins B₂+G₁ (AFB₂+G₁), ochratoxin A (OTA), [...] Read more.

The mechanisms by which yeast cells respond to environmental stress include the production of heat shock proteins (HSPs) and the reduction of oxidative stress. The response of yeast exposed to aflatoxins B₂+G₁ (AFB₂+G₁), ochratoxin A (OTA), and zearalenone (ZEA) in aerobic conditions was studied. After 72 h of yeast cultivation in media contaminated with mycotoxins, the growth of yeast biomass, the level of malondialdehyde, and the activity of superoxide dismutase, glutathione S-transferase and glutathione peroxidase were examined; the expression profile of the following heat shock proteins was also determined: HSP31, HSP40, HSP60, HSP70, and HSP104. It was demonstrated that at the tested concentrations, both AFB₂+G₁ and ZEA inhibited yeast biomass growth. OTA at a concentration of 8.4 [µg/L] raised the MDA level. Intensified lipoperoxidation and increased activity of SOD and GPx were observed, regardless of the level of contamination with ZEA (300 µg/L or 900 µg/L). Increased contamination with AFB₂+G₁ and OTA caused an increase in the production of most HSPs tested (HSP31, HSP40, HSP70, HSP104). ZEA contamination in the used concentration ranges reduced the production of HSP31. The response of yeast cells to the presence of mycotoxin as a stressor resulted in the expression of certain HSPs, but the response was not systematic, which was manifested in different profiles of protein expression depending on the mycotoxin used. The tested mycotoxins influenced the induction of oxidative stress in yeast cells to varying degrees, which resulted in the activation of mainly SOD without GST mobilization or with a small involvement of GPx. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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17 pages, 10017 KiB

Open AccessArticle

Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy

by Benedetta Caraba, Mariarita Stirpe, Vanessa Palermo, Ugo Vaccher, Michele Maria Bianchi, Claudio Falcone and Cristina Mazzoni

Int. J. Mol. Sci. 2023, 24(18), 13708; https://doi.org/10.3390/ijms241813708 - 5 Sep 2023

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Abstract

LSM4 is an essential yeast gene encoding a component of different LSM complexes involved in the regulation of mRNA splicing, stability, and translation. In previous papers, we reported that the expression in S. cerevisiae of the K. lactis LSM4 gene lacking the C-terminal [...] Read more.

LSM4 is an essential yeast gene encoding a component of different LSM complexes involved in the regulation of mRNA splicing, stability, and translation. In previous papers, we reported that the expression in S. cerevisiae of the K. lactis LSM4 gene lacking the C-terminal Q/N-rich domain in an Lsm4 null strain S. cerevisiae (Sclsm4Δ1) restored cell viability. Nevertheless, in this transformed strain, we observed some phenotypes that are typical markers of regulated cell death, reactive oxygen species (ROS), and oxidated RNA accumulation. In this paper, we report that a similar truncation operated in the S. cerevisiae LSM4 gene confers on cells the same phenotypes observed with the K. lactis lsm4Δ1 gene. Up until now, there was no evidence of the direct involvement of LSM4 in autophagy. Here we found that the Sclsm4Δ1 mutant showed a block in the autophagic process and was very sensitive to nitrogen starvation or treatment with low doses of rapamycin, an inducer of autophagy. Moreover, both during nitrogen starvation and aging, the Sclsm4Δ1 mutant accumulated cytoplasmic autophagy-related structures, suggesting a role of Lsm4 in a later step of the autophagy process. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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16 pages, 3122 KiB

Open AccessArticle

Sir2 and Glycerol Underlie the Pro-Longevity Effect of Quercetin during Yeast Chronological Aging

by Francesco Abbiati, Stefano Angelo Garagnani, Ivan Orlandi and Marina Vai

Int. J. Mol. Sci. 2023, 24(15), 12223; https://doi.org/10.3390/ijms241512223 - 31 Jul 2023

Cited by 1 | Viewed by 1540

Abstract

Quercetin (QUER) is a natural polyphenolic compound endowed with beneficial properties for human health, with anti-aging effects. However, although this flavonoid is commercially available as a nutraceutical, target molecules/pathways underlying its pro-longevity potential have yet to be fully clarified. Here, we investigated QUER [...] Read more.

Quercetin (QUER) is a natural polyphenolic compound endowed with beneficial properties for human health, with anti-aging effects. However, although this flavonoid is commercially available as a nutraceutical, target molecules/pathways underlying its pro-longevity potential have yet to be fully clarified. Here, we investigated QUER activity in yeast chronological aging, the established model for simulating the aging of postmitotic quiescent mammalian cells. We found that QUER supplementation at the onset of chronological aging, namely at the diauxic shift, significantly increases chronological lifespan (CLS). Consistent with the antioxidant properties of QUER, this extension takes place in concert with a decrease in oxidative stress. In addition, QUER triggers substantial changes in carbon metabolism. Specifically, it promotes an enhancement of a pro-longevity anabolic metabolism toward gluconeogenesis due to improved catabolism of C2 by-products of yeast fermentation and glycerol. The former is attributable to the Sir2-dependent activity of phosphoenolpyruvate carboxykinase and the latter to the L-glycerol 3-phosphate pathway. Such a combined increased supply of gluconeogenesis leads to an increase in the reserve carbohydrate trehalose, ensuring CLS extension. Moreover, QUER supplementation to chronologically aging cells in water alone amplifies their long-lived phenotype. This is associated with intracellular glycerol catabolism and trehalose increase, further indicating a QUER-specific influence on carbon metabolism that results in CLS extension. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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14 pages, 1645 KiB

Open AccessArticle

Defects in Mitochondrial Functions Affect the Survival of Yeast Cells Treated with Non-Thermal Plasma

by Anna Strížová, Paulína Šmátralová, Petra Chovančíková, Zdenko Machala and Peter Polčic

Int. J. Mol. Sci. 2023, 24(11), 9391; https://doi.org/10.3390/ijms24119391 - 28 May 2023

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Abstract

Exposure of living cells to non-thermal plasma produced in various electrical discharges affects cell physiology and often results in cell death. Even though plasma-based techniques have started finding practical applications in biotechnology and medicine, the molecular mechanisms of interaction of cells with plasma [...] Read more.

Exposure of living cells to non-thermal plasma produced in various electrical discharges affects cell physiology and often results in cell death. Even though plasma-based techniques have started finding practical applications in biotechnology and medicine, the molecular mechanisms of interaction of cells with plasma remain poorly understood. In this study, the involvement of selected cellular components or pathways in plasma-induced cell killing was studied employing yeast deletion mutants. The changes in yeast sensitivity to plasma-activated water were observed in mutants with the defect in mitochondrial functions, including transport across the outer mitochondrial membrane (∆por1), cardiolipin biosynthesis (∆crd1, ∆pgs1), respiration (ρ⁰) and assumed signaling to the nucleus (∆mdl1, ∆yme1). Together these results indicate that mitochondria play an important role in plasma-activated water cell killing, both as the target of the damage and the participant in the damage signaling, which may lead to the induction of cell protection. On the other hand, our results show that neither mitochondria-ER contact sites, UPR, autophagy, nor proteasome play a major role in the protection of yeast cells from plasma-induced damage. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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25 pages, 3369 KiB

Open AccessArticle

Integrative Analysis of the Ethanol Tolerance of Saccharomyces cerevisiae

by Ivan Rodrigo Wolf, Lucas Farinazzo Marques, Lauana Fogaça de Almeida, Lucas Cardoso Lázari, Leonardo Nazário de Moraes, Luiz Henrique Cardoso, Camila Cristina de Oliveira Alves, Rafael Takahiro Nakajima, Amanda Piveta Schnepper, Marjorie de Assis Golim, Thais Regiani Cataldi, Jeroen G. Nijland, Camila Moreira Pinto, Matheus Naia Fioretto, Rodrigo Oliveira Almeida, Arnold J. M. Driessen, Rafael Plana Simōes, Mônica Veneziano Labate, Rejane Maria Tommasini Grotto, Carlos Alberto Labate, Ary Fernandes Junior, Luis Antonio Justulin, Rafael Luiz Buogo Coan, Érica Ramos, Fabiana Barcelos Furtado, Cesar Martins and Guilherme Targino Valente Show full author list Hide full author list

Int. J. Mol. Sci. 2023, 24(6), 5646; https://doi.org/10.3390/ijms24065646 - 15 Mar 2023

Cited by 3 | Viewed by 2779

Abstract

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) [...] Read more.

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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Review

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22 pages, 3096 KiB

Open AccessReview

A Yeast Mitotic Tale for the Nucleus and the Vacuoles to Embrace

by Silvia Santana-Sosa, Emiliano Matos-Perdomo, Jessel Ayra-Plasencia and Félix Machín

Int. J. Mol. Sci. 2023, 24(12), 9829; https://doi.org/10.3390/ijms24129829 - 6 Jun 2023

Viewed by 2078

Abstract

The morphology of the nucleus is roughly spherical in most eukaryotic cells. However, this organelle shape needs to change as the cell travels through narrow intercellular spaces during cell migration and during cell division in organisms that undergo closed mitosis, i.e., without dismantling [...] Read more.

The morphology of the nucleus is roughly spherical in most eukaryotic cells. However, this organelle shape needs to change as the cell travels through narrow intercellular spaces during cell migration and during cell division in organisms that undergo closed mitosis, i.e., without dismantling the nuclear envelope, such as yeast. In addition, the nuclear morphology is often modified under stress and in pathological conditions, being a hallmark of cancer and senescent cells. Thus, understanding nuclear morphological dynamics is of uttermost importance, as pathways and proteins involved in nuclear shaping can be targeted in anticancer, antiaging, and antifungal therapies. Here, we review how and why the nuclear shape changes during mitotic blocks in yeast, introducing novel data that associate these changes with both the nucleolus and the vacuole. Altogether, these findings suggest a close relationship between the nucleolar domain of the nucleus and the autophagic organelle, which we also discuss here. Encouragingly, recent evidence in tumor cell lines has linked aberrant nuclear morphology to defects in lysosomal function. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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12 pages, 987 KiB

Open AccessReview

Light Stress in Yeasts: Signaling and Responses in Creatures of the Night

by Ilaria Camponeschi, Arianna Montanari, Cristina Mazzoni and Michele Maria Bianchi

Int. J. Mol. Sci. 2023, 24(8), 6929; https://doi.org/10.3390/ijms24086929 - 8 Apr 2023

Cited by 1 | Viewed by 1640

Abstract

Living organisms on the surface biosphere are periodically yet consistently exposed to light. The adaptive or protective evolution caused by this source of energy has led to the biological systems present in a large variety of organisms, including fungi. Among fungi, yeasts have [...] Read more.

Living organisms on the surface biosphere are periodically yet consistently exposed to light. The adaptive or protective evolution caused by this source of energy has led to the biological systems present in a large variety of organisms, including fungi. Among fungi, yeasts have developed essential protective responses against the deleterious effects of light. Stress generated by light exposure is propagated through the synthesis of hydrogen peroxide and mediated by regulatory factors that are also involved in the response to other stressors. These have included Msn2/4, Crz1, Yap1, and Mga2, thus suggesting that light stress is a common factor in the yeast environmental response. Full article

(This article belongs to the Special Issue Stress Response Research: Yeast as Models)

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