Untangling the Roles of Anti-Apoptosis in Regulating Programmed Cell Death using Humanized Yeast Cells

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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Induction of apoptosis in Saccharomyces cerevisiae results in the spontaneous maturation of tetravirus procapsids in vivo

Journal of General Virology ◽

10.1099/vir.0.82250-0 ◽

2007 ◽

Vol 88 (5) ◽

pp. 1576-1582 ◽

Cited By ~ 17

Author(s):

Michele Tomasicchio ◽

Philip Arno Venter ◽

Karl H. J. Gordon ◽

Terry N. Hanzlik ◽

Rosemary Ann Dorrington

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Death ◽

Programmed Cell Death ◽

Conformational Changes ◽

Yeast Cells ◽

Genomic Rnas ◽

Virus Like Particle ◽

Induced Apoptosis

The Tetraviridae are a family of small, non-enveloped, insect RNA viruses consisting of one or two single-stranded, positive-sense genomic RNAs encapsidated in an icosahedral capsid with T=4 symmetry. Tetravirus procapsids undergo maturation when exposed to a low pH environment in vitro. While the structural biology of the conformational changes that mediate acid-dependent maturation is well understood, little is known about the significance of acid-dependent maturation in vivo. To address this question, the capsid-coding sequence of the tetravirus Helicoverpa armigera stunt virus was expressed in Saccharomyces cerevisiae cells. Virus-like particles were shown to assemble as procapsids that matured spontaneously in vivo as the cells began to age. Growth in the presence of hydrogen peroxide or acetic acid, which induced apoptosis or programmed cell death in the yeast cells, resulted in virus-like particle maturation. The results demonstrate that assembly-dependent maturation of tetravirus procapsids in vivo is linked to the onset of apoptosis in yeast cells. We propose that the reduction in pH required for tetraviral maturation may be the result of cytosolic acidification, which is associated with the early onset of programmed cell death in infected cells.

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Abstract 2333: Genetic characterization of programmed cell death in aneuploid yeast cells

10.1158/1538-7445.am2018-2333 ◽

2018 ◽

Author(s):

Megan Onyundo ◽

Matthew Sanborn ◽

Victoria Timmel ◽

Nicanor Austriaco

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Genetic Characterization ◽

Yeast Cells

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

Biochemical Society Transactions ◽

10.1042/bst0391538 ◽

2011 ◽

Vol 39 (5) ◽

pp. 1538-1543 ◽

Cited By ~ 28

Author(s):

Nicoletta Guaragnella ◽

Lucia Antonacci ◽

Salvatore Passarella ◽

Ersilia Marra ◽

Sergio Giannattasio

Keyword(s):

Cell Death ◽

Acetic Acid ◽

Programmed Cell Death ◽

Time Course ◽

Reactive Oxygen Species Generation ◽

Yeast Cells ◽

Model Organisms ◽

Dependent Manner ◽

Cell Death Pathways ◽

Cyt C

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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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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