Editorial: Yeast cell aging and death.

A conspicuous amount of knowledge about the molecular biology of the cell has come from studies on yeast Saccharomyces cerevisiae, mostly because of its unrivaled qualities as a toolkit for molecular genetics study. The discovery in the late 90’s that this unicellular eukaryote alsomay activate cell death programs both physiologically, like mammalian apoptotic cell death (Madeo, Frohlich and Frohlich 1997), and under environmental stress, completed the yeast-toolkit. The first thematic issue on this topic of FEMS Yeast Research four years ago witnessed the noticeable amount of research carried out to get a deeper insight into the mechanisms of fundamental biological processes, already discovered in yeast, such as genetic stability and expression, cell cycle, organelle biogenesis and cross-talk. Indeed, it has been possible to study these processes with the added dimension to discover their function and interrelationships in cell homeostasis maintenance considering also the effect of environmental cues. Although debated by the scientific community, the field of yeast regulated cell death research has been expanding to more andmore bio-medical research themes, including aging, human diseases, cell stress response and metabolism. Research on ageing is one of the topmedical priorities in developed societies and yeast represents an attractive model system for studying more complex phenomena that occur in higher eukaryotic cells, including cell division, ageing and apoptosis. While such research in a clinical setting is confronted with—and limited by—ethical issues, and since studying ageing, longevity and regulated cell death in metazoan models is time consuming and costly, yeast cells offer an attractive eukaryotic model. Although it is now clear that yeast can indeed undergo cellular suicide, the corresponding terminology to describe this multifaceted process remains heterogeneous and potentially misleading. Thus, following the directions of the Nomenclature Committee on Cell Death (NCCD) and adapting them to the particularities of S. cerevisiae, the yeast cell death research community has recently proposed unified criteria for the definition of accidental, regulated and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria (Carmona-Gutierrez et al. 2018). This has clearly defined for the first time the concept of ‘yeast cell death’, with significant progress being made at the phenotypical and mechanistic levels, including the finding that, similarly to higher eukaryotes, yeast can also engage in distinct cell death modalities. The second scientific revolution of S. cerevisiae as a model organism for fundamental academic research as well as a biofactory for a wide range of industrial applications is already under way. On one hand, postgenomic systems biology research has been focusing on the global mapping of genetic interaction networks. The systematic analysis of trigenic interactions in yeast, invented and developed in the laboratory of Charles Boone at the University of Toronto, is definitely laying the basis for the first successful opportunity to modelling a cell (Kuzmin et al. 2018). On the other hand, the international Synthetic Yeast Genome Project, known as Yeast 2.0 or Sc2.0, is to create a fully manmade genome for S. cerevisiae in order to better understand the biological intricacies of eukaryotic semi-synthetic organisms. This will allow tomore accurately predict and control the practical outcomes of genome engineering—as opposed to individual gene-based genetic engineering (Pretorius 2017). Despite these promising developments, elucidation of the mechanisms and identification of molecules controlling the intricate network, which regulates cell homeostasis is still an urgent necessity, in order to fully grasp the benefits of a holistic approach to biomedical and biotechnological research. Thus, this thematic issue is a showcase for cutting-edge achievements in the knowledge on the molecular basis of many fundamental cellular processes governing cell homeostasis, thus highlighting the new age of yeast research in biomedicine and biotechnology. In particular, special attention is paid to molecular mechanisms of ageing and regulated cell death, pointing to yeast as a valuable model for studying the onset of diseases and for screening/design drugs able to interfere with these pathologies. In this second thematic issue on yeast aging and cell death of FEMS Yeast Research we have collected and edited six Mini Reviews that provide an overview of cutting-edge research on fundamental processes, including RNA stability, nutrient sensing, proteostasis, lipotoxicity, mitochondrial–cytosol–nucleus communications and aging. Threemini-reviews dealwith yeastmulticellular communities, the potential of yeast mitochondria to develop mitochondrial systems biology and the use of yeast as a platform for anti-aging drug discovery. Obesity and overweight are the adverse effects of excessive nutrition and they can be associated with metabolic alterations leading to metabolic syndrome. Although the exact etiology of metabolic syndrome is not known, unbalanced lipidmetabolism in non-adipose tissues is considered to contribute to lipotoxicity, The use of yeast has provided important insights into the toxicity associated with exposure to excess fatty acids (FAs), diacylglycerol (DGs), sterols and ceramides. The minireview by Rockenfeller and Gourlay (doi: 10.1093/femsyr/foy034) recapitulates recent research advances on the Rim101 pathway and membrane contact sites in the context of lipotoxicity in yeast and offers an outlook for future research directions.