Yeast apoptosis—From genes to pathways

Fröhlich, Kai‐Uwe; Fussi, Heike; Ruckenstuhl, Christoph

doi:10.1016/j.semcancer.2006.11.006

Cited by 73 publications

(62 citation statements)

References 104 publications

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“…S. cerevisiae has been employed as a "clean room" for investigating the interaction of proteins involved in apoptosis and PCD. Even if we now know that during yeast colony development, regulated cell death is essential for the long-term survival of the colony population, 28 this could explain why apoptosis is less complex in yeast than in pluricellular organisms. Conversely, autophagy is a mechanism directly involved in both survival and death at cellular level.…”

Section: Discussionmentioning

confidence: 99%

Identification of autophagy genes in Ciona intestinalis: A new experimental model to study autophagy mechanism

Godefroy¹,

Hoa²,

Tsokanos³

et al. 2009

Autophagy

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Programmed cell death (PCD) is a mechanism implicated in many physiological and pathological processes. Until recently, apoptosis (self-killing) was the most largely studied mechanism of PCD but a growing number of laboratories are now interested in autophagy (self-eating). In the past few years data showing a tight link between both pathways has accumulated. Until now our laboratory used Ciona intestinalis, a chordate model in which in vivo experiments are possible, to study apoptosis. Recently, we showed that autophagy also occurs in the development of Ciona intestinalis and that the specific markers of both types of death are found in the same tissues and/or in the same cells. These results drove us to postulate that Ciona intestinalis can be a good model to study the link between apoptosis and autophagy. In this article, we conducted an in silico study of autophagy genes. We explored the genomes of Ciona intestinalis, of the second ascidian Ciona savignyi, and those of the classical biological models (Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and Homo sapiens) to extract and compare autophagy gene sequences. This genomic study was completed by an analysis of: (i) mRNA profile expression during development and (ii) the localization of Beclin protein by immunofluorescent staining in the Ciona intestinalis larvae. Taken together, the results allowed us to conclude that a complex autophagic machinery is present in Ciona intestinalis. Actually, the number of autophagy genes in Ciona intestinalis is comparable to the number of autophagy genes in human.

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Section: Discussionmentioning

confidence: 99%

Identification of autophagy genes in Ciona intestinalis: A new experimental model to study autophagy mechanism

Godefroy¹,

Hoa²,

Tsokanos³

et al. 2009

Autophagy

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“…It has been proposed that apoptotic processes are useful in unicellular organisms for their survival under conditions of environmental stresses and are relevant in populations of cells such as colonies and biofilms (Skulachev, 2002;Buttner et al, 2006). Because of their powerful genetics, S. cerevisiae and S. pombe have become interesting models to study the core mechanisms of apoptosis (Ink et al, 1997;Ligr et al, 1998;Madeo et al, 2002;Priault et al, 2003;Hardwick and Cheng, 2004;Madeo et al, 2004;Rodriguez-Menocal and D'Urso, 2004;Burhans and Weinberger, 2007;Frohlich et al, 2007;Almeida et al, 2008;Fabrizio and Longo, 2008;Low and Yang, 2008).The molecular chaperone calnexin plays key roles in the translocation of nascent polypeptides and in the folding and quality control of newly synthesized proteins (Bukau et al, 2000;Fewell et al, 2001;Williams, 2006). Structurally, calnexin is a type I ER transmembrane protein, with a large lumenal domain, a transmembrane domain (TM), and a short cytosolic tail (see Figure 1A).…”

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confidence: 99%

Calnexin Is Involved in Apoptosis Induced by Endoplasmic Reticulum Stress in the Fission Yeast

Guérin

Arseneault

Dumont

et al. 2008

MBoC

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Stress conditions affecting the functions of the endoplasmic reticulum (ER) cause the accumulation of unfolded proteins. ER stress is counteracted by the unfolded-protein response (UPR). However, under prolonged stress the UPR initiates a proapoptotic response. Mounting evidence indicate that the ER chaperone calnexin is involved in apoptosis caused by ER stress. Here, we report that overexpression of calnexin in Schizosaccharomyces pombe induces cell death with apoptosis markers. Cell death was partially dependent on the Ire1p ER-stress transducer. Apoptotic death caused by calnexin overexpression required its transmembrane domain (TM), and involved sequences on either side of the ER membrane. Apoptotic death caused by tunicamycin was dramatically reduced in a strain expressing endogenous levels of calnexin lacking its TM and cytosolic tail. This demonstrates the involvement of calnexin in apoptosis triggered by ER stress. A genetic screen identified the S. pombe homologue of the human antiapoptotic protein HMGB1 as a suppressor of apoptotic death due to calnexin overexpression. Remarkably, overexpression of human calnexin in S. pombe also provoked apoptotic death. Our results argue for the conservation of the role of calnexin in apoptosis triggered by ER stress, and validate S. pombe as a model to elucidate the mechanisms of calnexin-mediated cell death. INTRODUCTIONThe endoplasmic reticulum (ER) is a specialized organelle playing essential and central roles in the biology of the cell. The ER is the site of synthesis and folding of secreted, membrane-bound and some organelle-targeted proteins (Bukau et al., 2000;Fewell et al., 2001). Protein folding in the ER is assisted by a battery of molecular chaperones and foldases (Bukau et al., 2000;Fewell et al., 2001;Trombetta and Parodi, 2003;Helenius and Aebi, 2004). In addition, the ER contains several factors required for optimum protein folding, including, ATP, Ca 2ϩ , and an oxidizing environment to allow disulphide-bond formation. Proper ER function is critical for numerous aspects of cell physiology, including vesicle trafficking and lipid and membrane biogenesis, as well as protein targeting and secretion (Lai et al., 2007).The ER is highly sensitive to stresses perturbing the cellular energy levels and ER lipid or glycolipid imbalances or changes in the redox state or Ca 2ϩ concentration (Breckenridge et al., 2003;Boyce and Yuan, 2006;Szegezdi et al., 2006). Such stresses reduce the protein folding capacity of the ER, which results in the accumulation and aggregation of unfolded proteins, a condition referred to as ER stress. When the capacity of the ER to fold proteins properly is compromised or overwhelmed, a highly conserved unfolded-protein response (UPR) signal-transduction pathway is activated. The ER response to stress is basically conserved from yeast to mammalian cells (Patil and Walter, 2001;Ron and Walter, 2007). To counter ER stress, the UPR halts general protein synthesis and up-regulates the transcription of genes encoding ER resident chaperone...

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“…Although yeast cells are capable of apoptosis, this process is little understood in other fungal pathogens, and to date, no components of the apoptotic pathway, including death receptors and their ligands, have been found on fungal cells (42). Therefore, it remains unclear whether NK cellinduced apoptosis plays a role in fungal damage.…”

Section: Mechanisms Of Direct Fungal Damage By Nk Cellsmentioning

confidence: 99%