Modeling Necroptotic and Pyroptotic Signaling in Saccharomyces cerevisiae.

Area of Science:

• Cellular Biology
• Immunology
• Genetics

Background:

• * *Saccharomyces cerevisiae* (yeast) is a key eukaryotic model organism.
• * Yeast facilitates understanding human genetic, molecular, and cellular biology, including diseases like cancer and aging.
• * Cell signaling pathways in human diseases are often studied in yeast.

Purpose of the Study:

• * To review strategies for developing humanized yeast models for studying regulated cell death (RCD).
• * To focus on RCD pathways related to innate immunity and inflammation, specifically pyroptosis and necroptosis.
• * To highlight yeast as a tool for studying these complex human pathways.

Main Methods:

• * Heterologous expression of mammalian innate immunity and inflammation pathway components in *S. cerevisiae*.
• * Utilizing yeast as a "cellular test tube" to study signaling complexes like the inflammasome and necrosome.
• * Investigating the function of enzymes (caspases, protein kinases) and effectors (Gasdermin D, MLKL).

Main Results:

• * Humanized yeast models allow for the study of mammalian RCD pathways, including pyroptosis and necroptosis.
• * These models facilitate the investigation of signaling complex assembly and enzyme activation.
• * The study demonstrates the utility of yeast in dissecting the properties and interactions of these pathways.

Conclusions:

• * Humanized yeast models are valuable tools for studying complex human cell death pathways.
• * Yeast provides a system to investigate innate immunity and inflammation mechanisms, aiding in the discovery of novel therapies.
• * Despite lacking native pathways, yeast's functional conservation enables the study of mammalian RCD.