Genetics of Apoptosis

7.

Regulators and applications of yeast apoptosis

Kai-Uwe Fröhlich and Frank Madeo

1.

Introduction

Apoptosis is a form of programmed cell death with a crucial role in the development
and maintenance of metazoan animals. Intense research has revealed a complex
network of regulators and effectors, which can be triggered by various toxins or
external signals (e.g., ethanol, reactive oxygen species [ROS], and receptor ligands)
and internal processes (e.g., mitotic catastrophe, replication failures, or
developmentally programmed cell death). Regulatory pathways and inducers vary
depending on tissue, developmental state, or host organism, resulting in diverse and
sometimes contradictory models for the regulation of apoptosis. A simple model
system, as in yeast, would be useful to clarify the dispute. However, apoptosis had
been assumed to be confined to multicellular animals. For a unicellular organism
such as yeast, a suicide mechanism seemed to be pointless, as it would result in the
death of the whole organism. When the complete genome sequence of the yeast
Saccharomyces cerevisiae became available in 1997, no relatives of the central players
in apoptosis, such as the caspases, members of the Bcl-2/Bax family, or Apaf-1, were
found, emphasizing the idea of a purely metazoan apoptosis.
It was a surprise, therefore, when cell death with the characteristics of apoptosis
was first described in unicellular organisms. The extensive use of yeast for apoptosis
research in very different areas of cell biology proves that the basic machinery of
apoptosis is indeed present and functional in yeast. The genes functioning in the cell
death of unicellular organisms have been confirmed as apoptotic regulators of
metazoans. These results promise easier access to an understanding of apoptosis.

2.

Expression of metazoan apoptotic genes induces cell death in

yeast

The first application of yeast for apoptosis research was its use in two-hybrid studies
to investigate the interactions between different apoptotic proteins. As an unexpected
side result, the expression of several proapoptotic genes, including bax (Greenhalf et