A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell.

In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging.DOI: http://dx.doi.org/10.7554/eLife.01883.001.

New approaches to an age-old problem.

Progress in the last decades indicated that ageing might be a universal fact of life. However, the molecular mechanisms underlying this process remain a major challenge in biology. Our relatively long life span and huge variations in lifestyle make detailed studies of ageing in humans difficult to interpret. In contrast, the relatively simple yeast Saccharomyces cerevisiae (budding yeast) has been a critical model in the field of ageing research for decades. Systems biology has contributed to the ageing field by mapping complex regulatory networks and resolving the dynamics of signal transduction pathways. In this review we first review the current understanding of ageing in yeast, then highlight the recent high-throughput systems and system biology approaches that could be used to further our understanding of ageing in yeast.