Comment on Severin, F.F., and Hyman, A.A. (2002). Pheromone Induces Programmed Cell Death in S. cerevisiae. Curr. Biol. 12, R233–R235

This paper by Severin and Hyman [1] is the first to connect the social biology of yeast to yeast apoptosis. Pheromones of the mating pathway trigger yeast apoptosis as marked by DNA fragmentation and generation of oxygen radicals. Disruption of cytochrome c protects the cells from alpha factor-induced apoptosis, suggesting the involvement of the mitochondrial apoptotic pathway. During preparation of their manuscript for publication, the authors unintentionally omitted some important references to yeast apoptosis. As the field of yeast apoptosis is growing very rapidly and is of interest to a broad readership, Current Biology and the authors felt it appropriate to clarify the priority. The authors show that Saccharomyces cerevisiae can induce 'what seems in outline to be similar to programmed cell death development in animal cells' [1]. An apoptotic phenotype of S. cerevisiae was first described by Madeo et al. [2] with various assays, including the TUNEL assay used by Severin and Hyman. In a similar approach Ludovico et al. [3] showed an apoptotic phenotype in yeast after treatment with acetic acid. Severin and Hyman report that the accumulation of reactive oxygen species is part of a potential yeast cell death programme. This has originally been shown by Madeo et al. [4]. One of the reagents used to detect reactive oxygen species was H2DCF-DA, which Severin and Hyman also use. It should be noted that most reports of apoptosis in yeast were subsequently linked to oxygen stress. In an overexpression screen based on apoptotic markers Ligr et al. [5] identified STM1 whose knockout confers resistance to H 2 O 2. Moon et al. [6] showed that the generation of oxygen radicals in yeast apoptosis can be suppressed by ascorbate peroxidase. Levine et al. [7] elucidated the mechanism by which yeast apoptosis can be modulated downstream of oxygen radicals. Laun et al. [8] showed that over-aged yeast cells undergo apoptosis, which is accompanied by accumulation of reactive oxygen species. These are just some examples and do not represent a complete list. Finally, Severin and Hyman state that cytochrome c release from mitochondria into the cytoplasm is a pathway conserved between mammalian and yeast cell death. This was first reported by Manon et al. [9], showing that heterologous expression of pro-apoptotic Bax induces cytochrome c release from the yeast mitochondria into the cytosol. A yeast mutant showing diagnostic markers of early and late apoptosis. (2001). Saccharomyces cerevisiae commits to a programmed …