Abstract

Cell death in response to distinct stimuli can manifest different morphological traits. It also depends on various cell death signaling pathways, extensively characterized in higher eukaryotes but less so in microorganisms. The study of cell death in yeast, and specifically Saccharomyces cerevisiae, can potentially be productive for understanding cell death, since numerous killing stimuli have been characterized for this organism. Here, we systematized the literature on external treatments that kill yeast, and which contains at least minimal data on cell death mechanisms. Data from 707 papers from the 7000 obtained using keyword searches were used to create a reference table for filtering types of cell death according to commonly assayed parameters. This table provides a resource for orientation within the literature; however, it also highlights that the common view of similarity between non-necrotic death in yeast and apoptosis in mammals has not provided sufficient progress to create a clear classification of cell death types. Differences in experimental setups also prevent direct comparison between different stimuli. Thus, side-by-side comparisons of various cell death-inducing stimuli under comparable conditions using existing and novel markers that can differentiate between types of cell death seem like a promising direction for future studies.

Highlights

  • Cell death is a non-reversible breakdown of the normal functions of a cell that is accompanied by division arrest and loss of homeostasis

  • It seems reasonable that a considerable Annexin+propidium iodide (PI)– population should be the best indicator of apoptotic death that was slow to progress to necrosis, while a large Annexin+PI+ population might be due to the rapid post-apoptosis secondary necrosis, or non-specific annexin staining

  • We were unable to make direct comparisons between various data, our compilation allows selection of interesting stimuli, which can be compared to each other side by side in future experimental work to determine the necrotic and non-necrotic ranges of cell death for different stimuli

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Summary

Introduction

Cell death is a non-reversible breakdown of the normal functions of a cell that is accompanied by division arrest and loss of homeostasis. While experiment-based systematic work is required to address these questions directly, the available literature provides a large swath of data, which could, potentially, be used to generate novel hypotheses and aim potential systematic research efforts This literature has not been grouped in a manner which is amenable to easy searching based on specific stimuli and the available data on the features of cell death observed in each case. This review supplies such a resource, performs preliminary analysis of the gathered data as well as provides a wide view of the different external factors that can kill yeast cells

Methods
Differential Hallmarks of Cell Death
Detection of PS Exposure
Yeast Metacaspase
Reduction of Cell Death by Cycloheximide Treatment
Lysosome- and Autophagy-Mediated Cell Death
Oxidative Stress and Reactive Oxygen Species
Calcium Signaling
Changes in the Functionality and Morphology of Organelles
Role of Treatment Severity in Determining Cell Death Type
Death-Inducing Perturbations in Yeast
Yeast Life Cycle Related Stimuli
Shocks of Physical Nature
Nutrient Imbalance and Depletion
Oxidants
Alcohols
Antimicrobial Peptides
Additional Compounds Used in Medicine and Agriculture
Discussion
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