Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells.

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.

journal_name

Cell

journal_title

Cell

authors

D'Angelo MA,Raices M,Panowski SH,Hetzer MW

doi

10.1016/j.cell.2008.11.037

subject

Has Abstract

pub_date

2009-01-23 00:00:00

pages

284-95

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(08)01512-2

journal_volume

136

pub_type

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