Programmed Cell Death Across the Eukaryotic Kingdoms

EU 6th Framework STREP

Research group of Kai-Uwe Fröhlich

Functional analyses of PCD regulators and their interactors in yeast




Fig.: Cell death pathways in yeast  

The Fröhlich laboratory discovered yeast (S. cerevisiae) cell death with the characteristics of apoptosis in a specific mutant of CDC48, coding for a protein involved in cell proliferation, membrane fusion, and retrograde ER transport. Heterologous expression of mammalian pro-apototic genes results in yeast apoptosis as well as various forms of environmental stress. As in animals, reactive oxygen species are important inducers of apoptosis in yeast and can be produced by the cell to act as second messengers of the cell death program. Searching for potential physiological situations of yeast cell death, the group found apoptotic death during replicative as well as chronological aging of yeast. Several yeast genes involved in the death program were then identified including orthologs of established apoptotic regulators in animals, most prominently yeast metacaspase. For others, no link to apoptosis had been described before, although orthologs of some of these have since been confirmed as apoptotic regulators in animals including CDC48 and VCP/p97 orthologs.

Relevant References

1) Madeo et al. (2002) A Caspase-Related Protease Regulates Apoptosis in Yeast. Mol Cell 9, 911-7
2) Ligr et al. (2001) The proteasomal substrate Stm1 participates in apoptosis-like cell death in yeast. Mol Biol Cell 12, 2422-32
3) Laun et al. (2001) Aged mother cells of S. cerevisiae show markers of oxidative stress & apoptosis. Mol Microbiol 39, 1166-73
4) Madeo et al. (1999) Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol 145, 757-67
5) Ligr et al. (1998) Mammalian Bax triggers apoptotic changes in yeast. FEBS Lett 438, 61-65

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