蛋白静止和内质网应激反应中的膜接触位点。

Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2025-07-28 eCollection Date: 2025-01-01 DOI:10.1177/25152564251363050
Febe Vermue, Aysegul Sapmaz, Ilana Berlin
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引用次数: 0

摘要

所有细胞功能的执行都依赖于一个健康的蛋白质组,其维护需要多模式的监督。大约三分之一的人类蛋白质存在于膜中,因此在生物发生和降解方面提出了独特的拓扑挑战。为了应对这些挑战,真核生物已经进化出了蛋白质折叠和质量控制的细胞器途径。大多数跨膜蛋白起源于内质网(ER),在内质网受到监视,必要时通过内质网相关的蛋白酶体降解(细胞质途径)或选择性自噬(ER-phagy;organellar途径)。在后一种情况下,内质网货物被运送到(内)溶酶体-通过内吞作用降解细胞表面分子的相同细胞器。在这里,我们概述了内质网和内溶酶体之间的动态协调,重点关注它们在称为膜接触位点(MCSs)的特殊物理界面中的作用。我们介绍了通过MCSs的跨室整合如何允许生物合成和蛋白水解细胞器微调彼此的膜组成、组织和动力学,并促进从蛋白质毒性应激中恢复。在此过程中,我们强调了细胞器生物学和蛋白质质量控制交叉路口的最新发展和悬而未决的问题,并将它们置于与膜稳态紊乱相关的因子特异性疾病的背景下。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Membrane Contact Sites in Proteostasis and ER Stress Response.

Execution of all cellular functions depends on a healthy proteome, whose maintenance requires multimodal oversight. Roughly a third of human proteins reside in membranes and thus present unique topological challenges with respect to biogenesis and degradation. To meet these challenges, eukaryotes have evolved organellar pathways of protein folding and quality control. Most transmembrane proteins originate in the endoplasmic reticulum (ER), where they are subject to surveillance and, if necessary, removal through either ER-associated proteasomal degradation (cytosolic pathway) or selective autophagy (ER-phagy; organellar pathway). In the latter case, ER cargoes are shuttled to (endo)lysosomes - the same organelles that degrade cell surface molecules via endocytosis. Here, we provide an overview of dynamic coordination between the ER and endolysosomes, with a focus on their engagement in specialized physical interfaces termed membrane contact sites (MCSs). We cover how cross-compartmental integration through MCSs allows biosynthetic and proteolytic organelles to fine-tune each other's membrane composition, organization, and dynamics and facilitates recovery from proteotoxic stress. Along the way, we highlight recent developments and open questions at the crossroads between organelle biology and protein quality control and cast them against the backdrop of factor-specific diseases associated with perturbed membrane homeostasis.

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