scholarly journals Regulation of Cell Death Induced by Acetic Acid in Yeasts

2021 ◽  
Vol 9 ◽  
Author(s):  
Susana R. Chaves ◽  
António Rego ◽  
Vítor M. Martins ◽  
Cátia Santos-Pereira ◽  
Maria João Sousa ◽  
...  
Keyword(s):  
Cell Death ◽  
Acetic Acid ◽  
Genetic Regulation ◽  
Industrial Applications ◽  
Research Field ◽  
Yeast Cells ◽  
Death Process ◽  
Regulated Cell Death ◽  
Molecular Events ◽  
The Impact

Acetic acid has long been considered a molecule of great interest in the yeast research field. It is mostly recognized as a by-product of alcoholic fermentation or as a product of the metabolism of acetic and lactic acid bacteria, as well as of lignocellulosic biomass pretreatment. High acetic acid levels are commonly associated with arrested fermentations or with utilization as vinegar in the food industry. Due to its obvious interest to industrial processes, research on the mechanisms underlying the impact of acetic acid in yeast cells has been increasing. In the past twenty years, a plethora of studies have addressed the intricate cascade of molecular events involved in cell death induced by acetic acid, which is now considered a model in the yeast regulated cell death field. As such, understanding how acetic acid modulates cellular functions brought about important knowledge on modulable targets not only in biotechnology but also in biomedicine. Here, we performed a comprehensive literature review to compile information from published studies performed with lethal concentrations of acetic acid, which shed light on regulated cell death mechanisms. We present an historical retrospective of research on this topic, first providing an overview of the cell death process induced by acetic acid, including functional and structural alterations, followed by an in-depth description of its pharmacological and genetic regulation. As the mechanistic understanding of regulated cell death is crucial both to design improved biomedical strategies and to develop more robust and resilient yeast strains for industrial applications, acetic acid-induced cell death remains a fruitful and open field of study.

scholarly journals Deletion of Atg22 gene contributes to reduce programmed cell death induced by acetic acid stress in Saccharomyces cerevisiae

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingjin Hu ◽  
Yachen Dong ◽  
Wei Wang ◽  
Wei Zhang ◽  
Hanghang Lou ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Cell Death ◽  
Cell Wall ◽  
Acetic Acid ◽  
Programmed Cell Death ◽  
Cell Wall Integrity ◽  
Yeast Cells ◽  
Death Process ◽  
Lignocellulosic Biofuel

Abstract Background Programmed cell death (PCD) induced by acetic acid, the main by-product released during cellulosic hydrolysis, cast a cloud over lignocellulosic biofuel fermented by Saccharomyces cerevisiae and became a burning problem. Atg22p, an ignored integral membrane protein located in vacuole belongs to autophagy-related genes family; prior study recently reported that it is required for autophagic degradation and efflux of amino acids from vacuole to cytoplasm. It may alleviate the intracellular starvation of nutrition caused by Ac and increase cell tolerance. Therefore, we investigate the role of atg22 in cell death process induced by Ac in which attempt is made to discover new perspectives for better understanding of the mechanisms behind tolerance and more robust industrial strain construction. Results In this study, we compared cell growth, physiological changes in the absence and presence of Atg22p under Ac exposure conditions. It is observed that disruption and overexpression of Atg22p delays and enhances acetic acid-induced PCD, respectively. The deletion of Atg22p in S. cerevisiae maintains cell wall integrity, and protects cytomembrane integrity, fluidity and permeability upon Ac stress by changing cytomembrane phospholipids, sterols and fatty acids. More interestingly, atg22 deletion increases intracellular amino acids to aid yeast cells for tackling amino acid starvation and intracellular acidification. Further, atg22 deletion upregulates series of stress response genes expression such as heat shock protein family, cell wall integrity and autophagy. Conclusions The findings show that Atg22p possessed the new function related to cell resistance to Ac. This may help us have a deeper understanding of PCD induced by Ac and provide a new strategy to improve Ac resistance in designing industrial yeast strains for bioethanol production during lignocellulosic biofuel fermentation.

Proteome and metabolome profiling of wild-type and YCA1 -knock-out yeast cells during acetic acid-induced programmed cell death

2015 ◽  
Vol 128 ◽  
pp. 173-188 ◽  
Author(s):  
Valentina Longo ◽  
Maša Ždralević ◽  
Nicoletta Guaragnella ◽  
Sergio Giannattasio ◽  
Lello Zolla ◽  
...  
Keyword(s):  
Cell Death ◽  
Acetic Acid ◽  
Programmed Cell Death ◽  
Yeast Cells ◽  
Wild Type ◽  
Knock Out ◽  
Metabolome Profiling

scholarly journals Ferrous-glutathione coupling mediates ferroptosis and frailty in Caenorhabditis elegans

2019 ◽  
Author(s):  
Nicole L. Jenkins ◽  
Simon A. James ◽  
Agus Salim ◽  
Fransisca Sumardy ◽  
Terence P. Speed ◽  
...  
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Ferrous Iron ◽  
Somatic Tissue ◽  
Glutathione Depletion ◽  
Death Process ◽  
C Elegans ◽  
Regulated Cell Death ◽  
Age Related ◽  
Ageing Rate

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed ferroptosis1, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in the Caenorhabditis elegans model of ageing2. Here we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan in C. elegans. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death process acting at specific life phases to induce organismal frailty, rather than contributing to a constant ageing rate. Because excess age-related iron elevation in somatic tissue, particularly in brain3–5, is thought to contribute to degenerative disease6, 7, our data indicate that post-developmental interventions to limit ferroptosis may promote healthy ageing.

scholarly journals Pkh1p-Ypk1p and Pkh1p-Sch9p Pathways Are Activated by Acetic Acid to Induce a Mitochondrial-Dependent Regulated Cell Death

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
António Rego ◽  
Filipa Mendes ◽  
Vítor Costa ◽  
Susana Rodrigues Chaves ◽  
Manuela Côrte-Real
Keyword(s):  
Cell Death ◽  
Acetic Acid ◽  
Cell Survival ◽  
Cell Fate ◽  
Negative Regulator ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Outer Membrane Permeabilization ◽  
Double Deletion ◽  
Regulated Cell Death ◽  
Single Deletion

The yeast Saccharomyces cerevisiae undergoes a mitochondrial-dependent regulated cell death (RCD) exhibiting typical markers of mammalian apoptosis. We have previously shown that ceramide production contributes to RCD induced by acetic acid and is involved in mitochondrial outer membrane permeabilization and cytochrome c release, especially through hydrolysis of complex sphingolipids catalyzed by Isc1p. Recently, we also showed that Sch9p regulates the translocation of Isc1p from the endoplasmic reticulum into mitochondria, perturbing sphingolipid balance and determining cell fate. In this study, we addressed the role of other signaling proteins in acetic acid-induced RCD. We found that single deletion of PKH1 or YPK1, as shown for SCH9 and ISC1, leads to an increase in cell survival in response to acetic acid and that Pkh1/2p-dependent phosphorylation of Ypk1p and Sch9p increases under these conditions. These results indicate that Pkh1p regulates acetic acid-induced RCD through Ypk1p and Sch9p. In addition, our results suggest that Pkh1p-Ypk1p is necessary for isc1Δ resistance to acetic acid-induced RCD. Moreover, double deletion of ISC1 and PKH1 has a drastic effect on cell survival associated with increased ROS accumulation and release of cytochrome c, which is counteracted by overexpression of the PKA pathway negative regulator PDE2. Overall, our results suggest that Pkh1p-Ypk1p and Pkh1p-Sch9p pathways contribute to RCD induced by acetic acid.

scholarly journals Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging Caenorhabditis elegans

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nicole L Jenkins ◽  
Simon A James ◽  
Agus Salim ◽  
Fransisca Sumardy ◽  
Terence P Speed ◽  
...  
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Ferrous Iron ◽  
Healthy Aging ◽  
Somatic Tissue ◽  
Glutathione Depletion ◽  
Death Process ◽  
Regulated Cell Death ◽  
Age Related ◽  
Cell Death Process

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed ferroptosis, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in Caenorhabditis elegans. Here, we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death process acting at specific life phases to induce organismal frailty, rather than contributing to a constant aging rate. Because excess age-related iron elevation in somatic tissue, particularly in brain, is thought to contribute to degenerative disease, post-developmental interventions to limit ferroptosis may promote healthy aging.

scholarly journals An Atlas of Phosphorylation and Proteolytic Processing Events During Excitotoxic Neuronal Death Reveals New Therapeutic Opportunities

2020 ◽  
Author(s):  
S. Sadia Ameen ◽  
Antoine Dufour ◽  
M. Iqbal Hossain ◽  
Ashfaqul Hoque ◽  
Sharelle Sturgeon ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Kinases ◽  
Neuronal Death ◽  
Neurological Disorders ◽  
Protein Modification ◽  
Neuronal Loss ◽  
Axonal Guidance ◽  
Death Process ◽  
Molecular Events

SummaryExcitotoxicity, a neuronal death process in neurological disorders, is initiated by over-stimulation of neuronal ionotropic glutamate receptors. The over-stimulated receptors dysregulate proteases, protein kinases and phosphatases, which in turn modify target neuronal proteins to induce cell death. To decipher this cell death mechanism, we used quantitative proteomics, phosphoproteomics and N-terminomics to identify modified proteins in excitotoxic neurons. Data, available in ProteomeXchange (identifiers: PXD019527 and PXD019211), enabled us to identify over one thousand such proteins with calpains, cathepsins and over twenty protein kinases as their major modifiers. These protein modification events can potentially perturb signalling pathways governing cell survival, synaptogenesis, axonal guidance and mRNA processing. Importantly, blocking the modification of Src protein kinase, a signalling hub in excitotoxic neurons, protected against neuronal loss in vivo in a rat model of neurotoxicity. Besides offering new insights into excitotoxic neuronal death mechanism, our findings suggest potential neuroprotective therapeutic targets for treating neurological disorders.Graphical abstractHighlightsMulti-dimensional proteomic analysis identified proteins modified by proteolysis and altered phosphorylation in neurons undergoing excitotoxic cell death.Calpains, cathepsins and over twenty protein kinases are major modifiers of these proteins.These protein modification events are predicted to impact cell survival, axonal guidance, synaptogenesis and mRNA processing.Blocking modification of an identified protein Src, which acts as a major signalling hub in neurons, was protective against excitotoxic injury in vivo.In BriefUsing multidimensional proteomic approaches, Ameen, et al. mapped the changes of proteome, phosphoproteome and N-terminome of cultured primary neurons during excitotoxicity, a crucial neuronal death process in neurological disorders. These proteomic changes document new excitotoxicity-associated molecular events, and offer insights into how these events are organized to induce neuronal death. Potential therapeutic relevance of these molecular events is illustrated by the demonstration that in vivo blockade of one of these events could protect against excitotoxic neuronal loss.

scholarly journals Mitochondrial active Ras2 protein promotes apoptosis and regulated cell death in a cAMP/PKA pathway-dependent manner in budding yeast.

2021 ◽  
Author(s):  
Barbara Bonomelli ◽  
Enzo Martegani ◽  
Sonia Colombo
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Death ◽  
Acetic Acid ◽  
Dependent Manner ◽  
Ras Proteins ◽  
Wild Type ◽  
High Affinity ◽  
Regulated Cell Death ◽  
Molecular Machinery ◽  
Pka Pathway

In previous papers, using the eGFP-RBD3 probe, which binds Ras-GTP with high affinity, we showed that activated Ras proteins are localized to the plasma membrane and in the nucleus in wild-type Saccharomyces cerevisiae cells growing exponentially on glucose, while an aberrant accumulation of activated Ras in mitochondria correlates to mitochondrial dysfunction, accumulation of ROS and an increase of apoptosis. In this paper, we show that lack of TPS1, which is known to trigger apoptosis in S. cerevisiae, induces localization of active Ras proteins in mitochondria, confirming the above-mentioned correlation. Next, by characterizing the ras1Δ and ras2Δ mutants concerning localization of active Ras proteins and propensity to undergo cell death, we show that active Ras2 proteins, which accumulate in the mitochondria following addition of acetic acid, a well-known pro-apoptotic stimulus, might be the GTPases involved in regulated cell death, while active Ras1 proteins, constitutively localized in mitochondria, might be involved in a pro-survival molecular machinery. Finally, by characterizing the gpa2Δ and cyr1Δ mutants concerning the propensity to undergo cell death, we show that active mitochondrial Ras proteins promote apoptosis through the cAMP/PKA pathway.

scholarly journals Blunted Fas signaling favors RIPK1-driven neutrophil necroptosis in critically ill COVID-19 patients

2021 ◽  
Author(s):  
Tiziano A Schweizer ◽  
Srikanth Mairpady Shambat ◽  
Clement Vulin ◽  
Sylvia Hoeller ◽  
Claudio Acevedo ◽  
...  
Keyword(s):  
Cell Death ◽  
Disease Severity ◽  
Critically Ill ◽  
Cytokine Profile ◽  
Caspase 8 ◽  
Potential Therapeutic Target ◽  
Regulated Cell Death ◽  
Cell Death Program ◽  
Fas Signaling ◽  
The Impact

Critically ill COVID-19 patients are characterized by a severely dysregulated cytokine profile and elevated neutrophil counts, which are thought to contribute to disease severity. However, to date it remains unclear how neutrophils contribute to pathophysiology during COVID-19. Here, we assessed the impact of the dysregulated cytokine profile on the tightly regulated cell death program of neutrophils. We show that in a subpopulation of neutrophils, canonical apoptosis was skewed towards rapidly occurring necroptosis. This phenotype was characterized by abrogated caspase-8 activity and increased RIPK1 levels, favoring execution of necroptosis via the RIPK1-RIPK3-MLKL axis, as further confirmed in COVID-19 biopsies. Moreover, reduction of sFas-L levels in COVID-19 patients and hence decreased signaling to Fas directly increased RIPK1 levels and correlated with disease severity. Our results suggest an important role for Fas signaling in the regulation of cell death program ambiguity via the ripoptosome in neutrophils during COVID-19 and a potential therapeutic target to curb inflammation and thus influence disease severity and outcome.

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