Abstract
In recent years, yeast was confirmed as a useful eukaryotic model system to decipher the complex mechanisms and networks occurring in higher eukaryotes, particularly in mammalian cells, in physiological as well in pathological conditions. This article focuses attention on the contribution of yeast in the study of a very complex scenario, because of the number and interconnection of pathways, represented by cell death. Yeast, although it is a unicellular organism, possesses the basal machinery of different kinds of cell death occurring in higher eukaryotes, i.e., apoptosis, regulated necrosis and autophagy. Here we report the current knowledge concerning the yeast orthologs of main mammalian cell death regulators and executors, the role of organelles and compartments, and the cellular phenotypes observed in the different forms of cell death in response to external and internal triggers. Thanks to the ease of genetic manipulation of this microorganism, yeast strains expressing human genes that promote or counteract cell death, onset of tumors and neurodegenerative diseases have been constructed. The effects on yeast cells of some of these genes are also presented.
Highlights
Regulated cell death (RCD) can be executed through distinct subroutines, sometime partially overlapping, leading to apoptosis, autophagy and programmed necrosis [1], and such scenarios have been described in yeast cells under physiological or induced stress conditions.In mammals, RCD can be observed during aging or in consequence of pathologies including neurodegenerative disorders, hypoxia and heart strokes
Yeast apoptosis was first described in cells carrying a mutated CDC48 gene, which codes for the AAA-ATPase and has roles in cell division, ubiquitin-dependent Endoplasmic reticulum (ER)-associated protein degradation (ERAD) and vesicle trafficking [2]
One of the first genes involved in yeast RCD was MCA1/ YCA1, which codes for a protein showing a caspase activity and plays an important role in regulating apoptosis in yeast
Summary
Regulated cell death (RCD) can be executed through distinct subroutines, sometime partially overlapping, leading to apoptosis, autophagy and programmed necrosis [1], and such scenarios have been described in yeast cells under physiological or induced stress conditions. RCD can be observed during aging or in consequence of pathologies including neurodegenerative disorders, hypoxia and heart strokes. Loss of RCD can result in the onset of cancer. Due to its simple handling, yeast represents a very useful eukaryotic model system for deciphering the complex network of the different and often interwoven RCD pathways occurring in mammals, aiming, in particular, to the identification of executors, to the role of cellular organelles and compartments, and to the detection of new cell phenotypes in response to external and internal triggers
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