Recent reports suggest that the yeastSaccharomyces cerevisiaecaspase-related metacaspase, Mca1, is required for cell-autonomous cytoprotective functions that slow cellular aging. Because the Mca1 protease has previously been suggested to be responsible for programmed cell death (PCD) upon stress and aging, these reports raise the question of how the opposing roles of Mca1 as a protector and executioner are regulated. One reconciling perspective could be that executioner activation may be restricted to situations where the death of part of the population would be beneficial, for example during colony growth or adaptation into specialized survival forms. Another possibility is that metacaspases primarily harbor beneficial functions and that the increased survival observed upon metacaspase removal is due to compensatory responses. Herein, we summarize data on the role of Mca1 in cell death and survival and approach the question of how a metacaspase involved in protein quality control may act as killer protein.
Single cell organisms contain ancestral homologues of caspases, called metacaspases, that can trigger programmed cell death. In this review, we consider how the yeast metacaspase, Mca1, required for proper protein quality control can act as both an executioner and cellular protector that can slow aging.