Developmentally Programmed Nuclear Destruction during Yeast Gametogenesis

Autophagy controls cellular catabolism in diverse eukaryotes and modulates programmed cell death in plants and animals. While studies of the unicellular yeast Saccharomyces cerevisiae have provided fundamental insights into the mechanisms of autophagy, the roles of cell death pathways in yeast are less well understood. Here, we describe widespread developmentally programmed nuclear destruction (PND) events that occur during yeast gametogenesis. PND is executed through apoptotic-like DNA fragmentation in coordination with an unusual form of autophagy that is most similar to mammalian lysosomal membrane permeabilization and mega-autophagy, a form of plant autophagic cell death. Undomesticated strains execute gametogenic PND broadly in maturing colonies to the apparent benefit of sibling cells, confirming its prominence during the yeast life cycle. Our results reveal that diverse cell-death-related processes converge during gametogenesis in a microbe distantly related to plants or animals, highlighting gametogenesis as a process during which programmed cell death mechanisms may have evolved. [Display omitted] [Display omitted] ► Discarded meiotic products are actively destroyed during gametogenesis ► Cleavage of genomic DNA into nucleosomal ladders by endonuclease G ► Nuclear protein destruction by mega-autophagy ► Wild yeast studies confirm the prominence of PND in the yeast life cycle Yeasts couple meiosis to the differentiation of long-lived gametes (spores). Eastwood et al. find that under reduced carbon conditions, a large fraction of meiotic nuclei are actively catabolized through mega-autophagy and endonuclease G pathways. These results suggest evolutionarily advantageous roles for “cell death” mechanisms in microbial reproduction.