Achievements and perspectives in yeast acetic acid-induced programmed cell death pathways

The use of non-mammalian model organisms, including yeast Saccharomyces cerevisiae, can provide new insights into eukaryotic PCD (programmed cell death) pathways. In the present paper, we report recent achievements in the elucidation of the events leading to PCD that occur as a response to yeast treatment with AA (acetic acid). In particular, ROS (reactive oxygen species) generation, cyt c (cytochrome c) release and mitochondrial function and proteolytic activity will be dealt with as they vary along the AA-PCD time course by using both wild-type and mutant yeast cells. Two AA-PCD pathways are described sharing common features, but distinct from one another with respect to the role of ROS and mitochondria, the former in which YCA1 acts upstream of cyt c release and caspase-like activation in a ROS-dependent manner and the latter in which cyt c release does not occur, but caspase-like activity increases, in a ROS-independent manner.

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

Journal of Proteomics ◽

10.1016/j.jprot.2015.08.003 ◽

2015 ◽

Vol 128 ◽

pp. 173-188 ◽

Cited By ~ 14

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

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

Biotechnology for Biofuels ◽

10.1186/s13068-019-1638-x ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 2

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.

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Silencing of BRCA2 decreases anoikis and its heterologous expression sensitizes yeast cells to acetic acid-induced programmed cell death

APOPTOSIS ◽

10.1007/s10495-014-1006-z ◽

2014 ◽

Vol 19 (9) ◽

pp. 1330-1341 ◽

Cited By ~ 3

Author(s):

Nicoletta Guaragnella ◽

Ersilia Marra ◽

Alvaro Galli ◽

Loredana Moro ◽

Sergio Giannattasio

Keyword(s):

Cell Death ◽

Acetic Acid ◽

Programmed Cell Death ◽

Heterologous Expression ◽

Yeast Cells

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Cytochrome c Release and Mitochondria Involvement in Programmed Cell Death Induced by Acetic Acid in Saccharomyces cerevisiae

Molecular Biology of the Cell ◽

10.1091/mbc.e01-12-0161 ◽

2002 ◽

Vol 13 (8) ◽

pp. 2598-2606 ◽

Cited By ~ 261

Author(s):

Paula Ludovico ◽

Fernando Rodrigues ◽

Agostinho Almeida ◽

Manuel T. Silva ◽

Antoni Barrientos ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Death ◽

Acetic Acid ◽

Cytochrome C ◽

Programmed Cell Death ◽

Yeast Cells ◽

Cytochrome C Release ◽

Apoptotic Pathway ◽

Enzymatic Assays ◽

Species Production

Evidence is presented that mitochondria are implicated in the previously described programmed cell death (PCD) process induced by acetic acid in Saccharomyces cerevisiae. In yeast cells undergoing a PCD process induced by acetic acid, translocation of cytochrome c (CytC) to the cytosol and reactive oxygen species production, two events known to be proapoptotic in mammals, were observed. Associated with these events, reduction in oxygen consumption and in mitochondrial membrane potential was found. Enzymatic assays showed that the activity of complexbc 1 was normal, whereas that of cytochrome c oxidase (COX) was strongly decreased. This decrease is in accordance with the observed reduction in the amounts of COX II subunit and of cytochromesa+a 3 . The acetic acid-induced PCD process was found to be independent of oxidative phosphorylation because it was not inhibited by oligomycin treatment. The inability ofS. cerevisiae mutant strains (lacking mitochondrial DNA, heme lyase, or ATPase) to undergo acetic acid-induced PCD and in the ATPase mutant (knockout in ATP10) the absence of CytC release provides further evidence that the process is mediated by a mitochondria-dependent apoptotic pathway. The understanding of the involvement of a mitochondria-dependent apoptotic pathway inS. cerevisiae PCD process will be most useful in the further elucidation of an ancestral pathway common to PCD in metazoans.

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Proteomic Analysis of Exosomes Released from Heatstressed Hepatocytes Reveals Promotion of Programmed Cell Death Pathways

SSRN Electronic Journal ◽

10.2139/ssrn.3279179 ◽

2018 ◽

Author(s):

Yue Li ◽

Xintao Zhu ◽

Guozhen Wang ◽

Huasheng Tong ◽

Xuguang Ling ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Proteomic Analysis ◽

Cell Death Pathways

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Translation machinery reprogramming in programmed cell death in Saccharomyces cerevisiae

Cell Death Discovery ◽

10.1038/s41420-020-00392-x ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Francesco Monticolo ◽

Emanuela Palomba ◽

Maria Luisa Chiusano

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Death ◽

Acetic Acid ◽

Programmed Cell Death ◽

Differential Expression ◽

Ribosomal Proteins ◽

Relative Proportion ◽

Duplication Event ◽

Genome Duplication Event ◽

Cell Death Pathway

AbstractProgrammed cell death involves complex molecular pathways in both eukaryotes and prokaryotes. In Escherichia coli, the toxin–antitoxin system (TA-system) has been described as a programmed cell death pathway in which mRNA and ribosome organizations are modified, favoring the production of specific death-related proteins, but also of a minor portion of survival proteins, determining the destiny of the cell population. In the eukaryote Saccharomyces cerevisiae, the ribosome was shown to change its stoichiometry in terms of ribosomal protein content during stress response, affecting the relative proportion between ohnologs, i.e., the couple of paralogs derived by a whole genome duplication event. Here, we confirm the differential expression of ribosomal proteins in yeast also during programmed cell death induced by acetic acid, and we highlight that also in this case pairs of ohnologs are involved. We also show that there are different trends in cytosolic and mitochondrial ribosomal proteins gene expression during the process. Moreover, we show that the exposure to acetic acid induces the differential expression of further genes coding for products related to translation processes and to rRNA post-transcriptional maturation, involving mRNA decapping, affecting translation accuracy, and snoRNA synthesis. Our results suggest that the reprogramming of the overall translation apparatus, including the cytosolic ribosome reorganization, are relevant events in yeast programmed cell death induced by acetic acid.

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The Novel ALG-2 Target Protein CDIP1 Promotes Cell Death by Interacting with ESCRT-I and VAPA/B

International Journal of Molecular Sciences ◽

10.3390/ijms22031175 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1175

Author(s):

Ryuta Inukai ◽

Kanako Mori ◽

Keiko Kuwata ◽

Chihiro Suzuki ◽

Masatoshi Maki ◽

...

Keyword(s):

Cell Death ◽

Essential Gene ◽

Susceptibility Gene ◽

Target Protein ◽

Hek293 Cells ◽

Dependent Manner ◽

Gene Encoding ◽

Endosomal Sorting ◽

Cell Death Pathways ◽

Apoptotic Protein

Apoptosis-linked gene 2 (ALG-2, also known as PDCD6) is a member of the penta-EF-hand (PEF) family of Ca2+-binding proteins. The murine gene encoding ALG-2 was originally reported to be an essential gene for apoptosis. However, the role of ALG-2 in cell death pathways has remained elusive. In the present study, we found that cell death-inducing p53 target protein 1 (CDIP1), a pro-apoptotic protein, interacts with ALG-2 in a Ca2+-dependent manner. Co-immunoprecipitation analysis of GFP-fused CDIP1 (GFP-CDIP1) revealed that GFP-CDIP1 associates with tumor susceptibility gene 101 (TSG101), a known target of ALG-2 and a subunit of endosomal sorting complex required for transport-I (ESCRT-I). ESCRT-I is a heterotetrameric complex composed of TSG101, VPS28, VPS37 and MVB12/UBAP1. Of diverse ESCRT-I species originating from four VPS37 isoforms (A, B, C, and D), CDIP1 preferentially associates with ESCRT-I containing VPS37B or VPS37C in part through the adaptor function of ALG-2. Overexpression of GFP-CDIP1 in HEK293 cells caused caspase-3/7-mediated cell death. In addition, the cell death was enhanced by co-expression of ALG-2 and ESCRT-I, indicating that ALG-2 likely promotes CDIP1-induced cell death by promoting the association between CDIP1 and ESCRT-I. We also found that CDIP1 binds to vesicle-associated membrane protein-associated protein (VAP)A and VAPB through the two phenylalanines in an acidic tract (FFAT)-like motif in the C-terminal region of CDIP1, mutations of which resulted in reduction of CDIP1-induced cell death. Therefore, our findings suggest that different expression levels of ALG-2, ESCRT-I subunits, VAPA and VAPB may have an impact on sensitivity of anticancer drugs associated with CDIP1 expression.

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