Poor old pores-The challenge of making and maintaining nuclear pore complexes in aging

Irina L. Rempel, Anton Steen, Liesbeth M. Veenhoff*

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    15 Citations (Scopus)
    158 Downloads (Pure)

    Abstract

    The nuclear pore complex (NPC) is the sole gateway to the nuclear interior, and its function is essential to all eukaryotic life. Controlling the functionality of NPCs is a tremendous challenge for cells. Firstly, NPCs are large structures, and their complex assembly does occasionally go awry. Secondly, once assembled, some components of the NPC persist for an extremely long time and, as a result, are susceptible to accumulate damage. Lastly, a significant proportion of the NPC is composed of intrinsically disordered proteins that are prone to aggregation. In this review, we summarize how the quality of NPCs is guarded in young cells and discuss the current knowledge on the fate of NPCs during normal aging in different tissues and organisms. We discuss the extent to which current data supports a hypothesis that NPCs are poorly maintained during aging of nondividing cells, while in dividing cells the main challenge is related to the assembly of new NPCs. Our survey of current knowledge points toward NPC quality control as an important node in aging of both dividing and nondividing cells. Here, the loss of protein homeostasis during aging is central and the NPC appears to both be impacted by, and to drive, this process.

    Original languageEnglish
    Pages (from-to)1058-1075
    Number of pages18
    JournalThe FEBS Journal
    Volume287
    Issue number6
    DOIs
    Publication statusPublished - 23-Jan-2020

    Keywords

    • chronological aging
    • nuclear pore complex assembly
    • nucleocytoplasmic transport
    • replicative aging
    • NUCLEOCYTOPLASMIC TRANSPORT DEFECTS
    • REPLICATIVE LIFE-SPAN
    • SACCHAROMYCES-CEREVISIAE
    • ASYMMETRIC SEGREGATION
    • MEMBRANE-PROTEINS
    • NONSPECIFIC COMPETITION
    • OXIDATIVE STRESS
    • DAMAGED PROTEINS
    • FG-NUCLEOPORINS
    • SKELETAL-MUSCLE

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