Dead cells bind dye nonspecifically.
Yeast do die of causes other than old age, but it remains unclear whether this death is like mammalian apoptosis, and to what extent it is controlled rather than a direct result of an insult to the cell. Apoptosis was put forward as a possibility when a caspase-like protein, Yca1p, was discovered, and dying cells were found to bind a caspase substrate.
But on page 311, Wysocki and Kron bring these conclusions, and the whole concept of yeast apoptosis, into doubt. Using yeast that are irreversibly arrested because of exposed telomeres, they find that it is the fluorophore, not the attached caspase substrate, that is binding the dying cells. Death does not require either Yca1p or the production of reactive oxygen species (ROS). Wysocki and Kron conclude that the cells are probably popping because of extended cell cycle arrest, although runaway autophagy remains a possibility.
The authors emphasize that apoptosis or other forms of programmed cell death may well occur, but that better evidence is needed. Kron says he would be convinced by a pathway that is activated before the onset of death and that can cause death when turned on in the absence of any cellular insult. Otherwise, he says, we are stuck with death via explosion—“the ultimate disappointing, dumb answer.” ▪