This puts ROS at a central position in yeast apoptosis. Yeast cells are also more
sensitive to H 2 O 2 -induced apoptosis when vesicle fusion is blocked (Levine et al.,
2001). Hence CDC48 mutation might trigger apoptosis in two distinct, synergistic
ways: generation of radicals and arrest of vesicle fusion.
Adenovirus E4orf4 protein has been reported to induce p53-independent apoptosis
in transformed mammalian cells. By heterologous expression of human E4orf4,
Kornitzer et al. (2001) could induce cell death in yeast by an irreversible growth arrest
at the G 2 /M transition accompanied by accumulation of ROS. E4orf4 expression in
mammalian cells also leads to accumulation of ROS and induces G 2 /M arrest prior
Figure 1. Facets of dying yeast.
Dihydrorhodamine 123 staining (A) reveals that some cells produce reactive oxygen to induce
apoptosis. (B) shows the same region in phase contrast. Apoptotic chromatin condensation
can be visualized by DAPI staining (C) or by electron microscopy (E). Staining with FITC-
labeled annexin V lights up the cytoplasmic membrane of protoplasted yeast cells (cell wall
removed enzymatically) early in apoptosis (D). The black nuclei in the TUNEL test indicate
massive DNA fragmentation in apoptotic yeast (F).
REGULATORS AND APPLICATIONS OF YEAST APOPTOSIS 145