Conspiracy of yeast killers: The fifth international meeting on yeast apoptosis in Prague, Czech Republic, 3–7 September, 2006

It was a unique atmosphere when 60 birds of paradise from all over the world gathered in Kutna Hora, an old silver-digger town near Prague. No justifications, no explanations, no excuses regarding the decision to work on such an exotic topic were offered. Instead, the community, which is almost a family since a core group of people and a growing number of others meet regularly to offer advice and help with plasmids and strains, suddenly realized that a turning point in the field had been reached. Prior to this meeting, most publications had demonstrated that yeast apoptosis (Madeo, 1997) is comparable to mammalian apoptosis. Here, for the first time, the majority of groups presented results that provided new insights into apoptosis research as a whole and that could give new directions to research in other model organisms or cell-culture systems. Chronological ageing of yeast, defined as the lifespan of a postdiauxic but still metabolic active culture, has been used as a valuable model with which to study oxidative damage and molecularly conserved ageing pathways of postmitotic tissues in higher organisms. Replicative ageing, defined by the number of daughters born from a single mother, represents a model for asymmetrically dividing stem cells. Both replicative and chronological ageing of yeast cells have been demonstrated to culminate in cell death with an apoptotic phenotype (Laun, 2001; Fabrizio, 2004; Herker, 2004). It was Ian Dawes (Sydney, Australia) who opened the meeting with an introduction about how reactive oxygen species (ROS) contribute to ageing by damaging nucleic acids, proteins and lipids. In addition, he gave details of a study aiming to evaluate the influence of diverse antioxidants on replicative lifespan and discussed the correlation between oxidative stress and replicative ageing (Laun, 2001). On a more methodological level, David Goldfarb (Rochester, USA) presented the development and initial applications of a new assay for determining replicative lifespan (‘death of daughters’ assay). Here, a genetically engineered yeast strain is used in which the daughters of mother cells die under nonpermissive conditions limiting replicative lifespan to the initial population of mother cells (Jarolim, 2004). He reported on the use of the assay to identify new genes that are required for full lifespan. Gennaro D'Urso (Miami, USA) showed how the method of apoptosis induction by chronological ageing is transferable to fission yeast. Data from this method suggest that DNA replication stress under starvation conditions may be responsible for activation of the cell-death pathway. In a different ageing approach, Kai-Uwe Fröhlich and Christoph Ruckenstuhl (Graz, Austria) presented a new monocolony assay to monitor developmental cell death within whole colonies. Interestingly, mitochondria, the central death-regulating organelles, appear to play a crucial role for cell survival in yeast colonies. Stefan Woelfl and Ana Kitanovic (Heidelberg, Germany) focused on cellular adaptive responses to low doses of toxic substances. In their study, low concentrations of MMS, a DNA-alkylating and thus DNA-damaging agent, triggered an adaptive response induced by the onset of the general stress response mechanism, an increased ROS production, and an intensified metabolic rate. However, this defence response, although it leads to an effective DNA damage repair, also shortens the life-span of the cells. Kitanovic & Wolfl (2006) further demonstrated that regulation of the key enzyme of gluconeogenesis, FBP1, is essential for such a proper response to DNA damage and ageing. Furthermore, rapid ageing upon Fbp1p-overexpression and a requirement for Yca1p or Aif1p, two key players of yeast apoptosis (Madeo, 2002; Wissing, 2004), in this process were shown. Paola Fabrizio (Los Angeles, USA) described a cell death and ageing regulatory network connecting mutations in yeast orthologues of mammalian Ras, Akt and Tor with resistance to stress-induced and age-dependent cell death. These results are beginning to reveal the complexity of a network of proteins involved in the regulation of both ageing and age-dependent cell death conserved from yeast to higher eukaryotes. Peter Hauptmann (Regensburg, Germany) presented a new, Yca1p-independent protease involved in cell death induced by defective N-glycosylation and acetic acid. Although cell death induced by N-glycosylation defects was accompanied by caspase-like activity, this activity seemed to be independent of YCA1. Instead, deletion of the protease KEX1 decreased the caspase-like activity, inhibited ROS formation, and improved cell survival (Hauptmann, 2006). The influence of acetic acid on induced cell death was also reported by Paula Ludovico from Braga, Portugal (Ludovico, 2002). Tobias Eisenberg (Graz, Austria) showed that polyamines promote yeast longevity and could provide the first insights into the mechanism behind it. Daniela Ehehalt (Stuttgart, Germany) delineated perturbations in calcium and manganese homeostasis as inducers of ER stress and programmed cell death in yeast. Heat stress caused impaired degradation of ER-luminal malfolded glycoproteins and subsequent death in cells deleted in PMR1, an ion pump for Ca2+ and Mn2+ uptake, which could be suppressed by the addition of calcium but not of manganese. This ER-linked death program required yeast metacaspase YCA1 and was most pronounced in Δpmr1Δaif1 cells, documenting also the protective role of the yeast apoptosis-inducing factor AIF1. Autophagy(definition) is a major intracellular-degradation process that plays a crucial role in survival during starvation in organisms ranging from yeast to mammals. Although autophagy is generally considered to be a nonselective process, selective forms of it have been shown to be involved in the degradation of several organelles. Using lactate-grown yeast subjected to nitrogen starvation, Ingrid Kiššová (Bordeaux, France) was able to provide evidence for selective as well