Yeast Dying to Survive

Abstract

There is evidence that unicellular organisms, yeast in particular, can undergo programmed cell death through a biochemical pathway with similarities to the apoptosis machinery of multicellular organisms. However, the evolutionary advantage of programmed cell death to a unicellular organism is not obvious (to say the least), leading some investigators to question the validity of a yeast programmed cell death pathway. Ivanovska and Hardwick provide an argument in favor of the biological relevance of such a death pathway in the context of cells infected with killer viruses, where the death program may benefit the community rather than a single cell. Most yeast strains are infected with viruses. One common group of double-stranded RNA virus, the M viruses, cause death of uninfected cells but provide immunity to infected cells (through an unknown mechanism). Ivanovska and Hardwick found that such killing appears to rely on components similar to those of apoptotic pathways in higher organisms. In particular, loss of the Fis1 protein, a protein that is thought to function in control of mitochondrial permeability, as do mammalian Bcl-2 family proteins, made cells more susceptible to cell death in an assay of uninfected cells cultured with cells infected with the M1 killer virus. Other components also proposed to mediate a yeast cell death pathway--Yca1, a metacaspase with similarity to mammalian caspases, and Tok1, a plasma membrane potassium channel--were shown to mediate cell death caused by the M1 virus. The M1 virus encodes a toxin, K1. Under proper culture conditions, K1 itself could cause programmed cell death, but through a separate pathway independent of the Yca1 metacaspase. In experiments with long culture conditions designed to simulate competition for survival in the wild, killer virus-infected cells overran cultures with noninfected cells. The authors propose that a primitive mechanism that distinguishes "self" (infected) and "nonself" (uninfected) cells may be evolutionarily advantageous in providing nutrients from the dying cells that enhance survival of the population of cells harboring the killer virus. I. Ivanovska, J. M. Hardwick, Viruses activate a genetically conserved cell death pathway in a unicellular organism. J. Cell Biol. 170 , 391-399 (2005). [Abstract] [Full Text]