Programmed Cell Death is Intrinsic to Yeast Gametogenesis

Studies of the yeast Saccharomyces cerevisiae have provided many critical insights into fundamental eukaryotic cell biology. Programmed cell death (PCD) is integral to animal and plant development, contributing to tissue homeostasis and morphogenesis by removing unneeded cells. Although PCD is of widespread importance to many organisms, studies of yeast have provided relatively limited insight into the mechanisms and physiological roles of PCD. Investigations of yeast cell death pathways have almost exclusively been restricted to cells undergoing vegetative growth, leaving no exploration of their potential functions during developmental transitions in the yeast life cycle. Here, I characterize a novel PCD intrinsic to yeast gametogenesis, or sporulation. Upon sporulation induction under severe carbon limitation, yeast cells subject only a fraction of their potential gametes to spore differentiation. Meiotic products which are not subject to spore development are shown to adopt an alternative fate of programmed destruction. I characterize the elimination of aborted gametes as programmed nuclear destruction (PND), a phenomenon which exhibits hallmarks of animal and plant PCD. Cells executing PND display fragmentation of genomic DNA by endonuclease G, a hallmark of animal apoptosis. The destruction of nuclear protein during PND is mediated by vacuolar proteases which undergo programmed release from the vacuole during sporulation. To understand the mechanisms underlying PND, I consider PND as part of a broader cell death program executing the demise of the meiotic mother cell. Accordingly, I find that the mother cell adopts characteristics of a dying cell following meiosis, including mitochondrial depolarization, vacuolar swelling and the loss of plasma membrane integrity. The timely execution of the mother cell depends on the development of its daughter spores, as cells lacking regulators of spore morphogenesis are unable to execute mother cell demise normally. As an extension of my studies of PCD, I also present preliminary, unanticipated evidence that Nuc1 contributes to mitochondrial genome metabolism. Overall, I propose that PCD of the meiotic mother cell is an intrinsic aspect of yeast gametogenesis which shares common genetic regulation with spore morphogenesis.Ph.D