TY - JOUR TI - Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics AU - Rempel, Irina L AU - Crane, Matthew M AU - Thaller, David J AU - Mishra, Ankur AU - Jansen, Daniel PM AU - Janssens, Georges AU - Popken, Petra AU - Akşit, Arman AU - Kaeberlein, Matt AU - van der Giessen, Erik AU - Steen, Anton AU - Onck, Patrick R AU - Lusk, C Patrick AU - Veenhoff, Liesbeth M A2 - Weis, Karsten A2 - Akhmanova, Anna VL - 8 PY - 2019 DA - 2019/06/03 SP - e48186 C1 - eLife 2019;8:e48186 DO - 10.7554/eLife.48186 UR - https://doi.org/10.7554/eLife.48186 AB - Nuclear transport is facilitated by the Nuclear Pore Complex (NPC) and is essential for life in eukaryotes. The NPC is a long-lived and exceptionally large structure. We asked whether NPC quality control is compromised in aging mitotic cells. Our images of single yeast cells during aging, show that the abundance of several NPC components and NPC assembly factors decreases. Additionally, the single-cell life histories reveal that cells that better maintain those components are longer lived. The presence of herniations at the nuclear envelope of aged cells suggests that misassembled NPCs are accumulated in aged cells. Aged cells show decreased dynamics of transcription factor shuttling and increased nuclear compartmentalization. These functional changes are likely caused by the presence of misassembled NPCs, as we find that two NPC assembly mutants show similar transport phenotypes as aged cells. We conclude that NPC interphase assembly is a major challenge for aging mitotic cells. KW - nuclear pore complex assembly KW - replicative aging KW - protein complex stoichiometry KW - nuclear transport KW - microfluidics KW - nuclear envelope herniation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -