European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, The Netherlands.
FEBS J. 2020 Mar;287(6):1058-1075. doi: 10.1111/febs.15205. Epub 2020 Jan 23.
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.
核孔复合体（NPC）是进入细胞核内部的唯一途径，其功能对所有真核生物都是至关重要的。控制 NPC 的功能对细胞来说是一个巨大的挑战。首先，NPC 是大型结构，其复杂的组装偶尔会出错。其次，一旦组装完成，NPC 的一些组件会持续很长时间，因此容易积累损伤。最后，NPC 的很大一部分由固有无序的蛋白质组成，这些蛋白质容易聚集。在这篇综述中，我们总结了 NPC 的质量在年轻细胞中是如何被保护的，并讨论了目前关于 NPC 在不同组织和生物体正常衰老过程中的命运的知识。我们讨论了目前的数据在多大程度上支持这样一种假设，即在非分裂细胞衰老过程中 NPC 维护不佳，而在分裂细胞中，主要的挑战与新 NPC 的组装有关。我们对现有知识的调查表明，NPC 质量控制是分裂和非分裂细胞衰老的一个重要节点。在这里，衰老过程中蛋白质平衡的丧失是核心，而 NPC 似乎既受到这一过程的影响，又推动了这一过程。
