Age-Dependent Deterioration of Nuclear Pore Complexes Causes a Loss of Nuclear Integrity in Postmitotic Cells

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.11.037 Byline: Maximiliano A. D'Angelo (1), Marcela Raices (1), Siler H. Panowski (1), Martin W. Hetzer (1) Keywords: CELLBIO; HUMDISEASE; DEVBIO Abstract: In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC components, like Nup153 and Nup50, are continuously exchanged, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire cellular life span. Besides the lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs, leading to an increase in nuclear permeability and the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear 'leakiness' is dramatically accelerated during aging and that a subset of nucleoporins is oxidatively damaged in old cells suggests that the accumulation of damage at the NPC might be a crucial aging event. Author Affiliation: (1) Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA Article History: Received 20 May 2008; Revised 5 October 2008; Accepted 21 November 2008 Article Note: (miscellaneous) Published: January 22, 2009