Poor old pores: The cell’s challenge to make and maintain nuclear pore complexes in aging

Nuclear pore complexes (NPCs) are among the largest protein complexes in the eukaryotic cell and are evolutionary conserved. The key function of NPCs is to facilitate nucleocytoplasmic exchange, as the main gateways to the nucleus. In this thesis, we have studied NPCs, NPC assembly, NPC maintenance and nucleocytoplasmic transport in the context of aging in baker’s yeast. We find, that mitoticallly aging cells show a decreased abundance of FG-Nups at the whole cell level and at the NE. We further analyze the abundance of proteins that assist in NPC assembly in aging and find, that several proteins decrease in abundance in aging. This decrease in the NPC assembly machinery, and potentially the FG-Nups is probably sufficient to cause the signs of NPC assembly problems that we observe during mitotic aging. Subsequently, we analyzed nucleocytoplasmic transport in replicative aging cells and find that nucleocytoplasmic exchange is slowed down during replicative aging, suggesting, that misassembled NPCs are not able to facilitate nucleocytoplasmic exchange. We conclude that the NPC assembly machinery is particularly challenged in mitotically aging cells.