Paper ID: 260
ETH Zürich (Switzerland)
Since several decades, budding yeast has proven to be a useful system to study the process of replicative ageing in eukaryotes. Indeed, yeast cells divide constitutively asymmetrically by growing a future daughter cell in the form of a bud at the surface of the mother cell. Interestingly, whereas the mother cell is ageing over time as established by the fact that it can only bud a limited number of times, the large majority of the daughters are born rejuvenated and enjoy the same lifespan potential as their mothers, irrespective of the age of their mother when they were produced. Interestingly, several hallmarks of ageing are conserved from yeast to metazoans, including the accumulation of protein aggregates in the ageing mother cell. Here I will report on our efforts to understand what these aggregates are, how they might contribute to ageing and how they are confined into the mother cell.
A widely shared view about age-associated protein aggregates is that they are formed due to protein misfolding and a decay in protein quality control as the cell age. Investigating this possibility, we have acquired hints that it might not always be the case. Indeed, cells carrying such an aggregate show no deficit in resorbing the Q-bodies forming upon heat-shock comparted to young cells. Similarly, they show no defect in ubiquitin-mediated protein degradation, excluding the possibility that aggregate form due to a functional weakening of this degradation pathway. In contrast, we have accumulated evidence that yeast cells aggregate specific proteins into super-assemblies in response to external signals as a mean to store information and adapt to environment. These protein aggregation processes contribute to ageing of the cell. I will discuss how they might do so, and how the mother cell ensures that these aggregates are not passed on to the next generation.