Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in post-mitotic cells

• Published in: Cell 2009-01, Vol.136 (2), p.284-295
• Main Authors: D’Angelo, Maximiliano A., Raices, Marcela, Panowski, Siler H., Hetzer, Martin W.
• Format: Article
• Language: English
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2008.11.037

In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of these multi-protein transport channels in post-mitotic cells, where the mitotic renewal of pores is absent, is unknown. Here we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of nuclear pore components, like Nup153 and Nup50, are continuously exchanged at the NPC, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire lifespan of a cell. In addition to a lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs leading to a loss of the nuclear permeability barrier and the leaking of cytoplasmic proteins into the nuclear compartment. Our finding that nuclear ‘leakiness’ is dramatically accelerated during aging and that a subset of nucleoporins are found to be oxidatively damaged in old cells, suggest that the accumulation of damage at the NPC structure might be a crucial event in age-related loss of nuclear integrity.