FAM134B介导的内质网自噬及其与疾病的关系

张艺; 魏娜

doi:10.16766/j.cnki.issn.1674-4152.003303

FAM134B介导的内质网自噬及其与疾病的关系

doi: 10.16766/j.cnki.issn.1674-4152.003303

张艺¹,
魏娜^{1, 2, ,}

1.
贵州医科大学病理学教研室，贵州贵阳 550004
2.
贵州医科大学附属医院病理科，贵州贵阳 550004

基金项目:

国家自然科学基金项目 U1812403-6-1-6

贵州省科技计划项目黔科合基础-ZK[2022]一般439

地方病与少数民族疾病教育部重点实验室(贵州医科大学)开放项目 FZSW-2021-007

详细信息

通讯作者:
魏娜，E-mail：1838228300@qq.com

中图分类号: R329.28
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- 文章访问数: 178
- HTML全文浏览量: 58
- PDF下载量: 12
- 被引次数: 0
出版历程
- 收稿日期: 2023-03-23
- 网络出版日期: 2024-01-29

FAM134B-mediated endoplasmic reticulum autophagy and its association with diseases

ZHANG Yi¹,
WEI Na^{1, 2
, ,}

1.
Department of Pathology, Guizhou Medical University, Guiyang, Guizhou 550004, China

摘要

摘要: 自噬能够降解损伤衰老的细胞器以及异常的蛋白质，能够给机体的生命活动提供部分所需的能量及原料。自噬主要分为4个阶段，包括自噬前体、自噬小体、自噬溶酶体的形成以及溶酶体水解酶降解自噬体内所包裹的大分子物质的过程，依赖溶酶体降解系统进行。在细胞内，内质网是最大的细胞器，蛋白质在内质网合成和加工，钙离子贮存在内质网中；蛋白质折叠错误、钙离子平衡失调会导致内质网功能紊乱，激活内质网自噬。自噬能够维持细胞稳态，选择性自噬和非选择性自噬是根据降解底物特异性的有无分成的2种自噬类型。内质网自噬是选择性自噬众多类型中的一种，是由内质网受体介导的自噬。序列相似性家族134成员B(FAM134B)是最先在哺乳动物中发现的且已被鉴定的内质网自噬受体，其介导的内质网自噬参与了众多疾病的发展进程。FAM134B通过LC3相互作用域和网状同源结构域诱导内质网膜弯曲碎片化，便于运输到溶酶体，促进内质网降解。适度的内质网自噬肃清破损的内质网，恢复内质网内稳态；而当内质网自噬过度时就会诱导细胞启动凋亡程序。一般情况下，机体低水平的自噬对于细胞的存活是有益的，而应激状态下的过度自噬或自噬功能障碍则对机体有害。本文介绍了自噬、内质网结构及其功能、内质网自噬以及FAM134B如何介导内质网自噬，并通过梳理相关文献，阐述了FAM134B介导的内质网自噬与神经系统疾病、消化系统疾病、心血管疾病、感染性疾病之间的联系，表明通过调控FAM134B的表达在一定程度上能够控制内质网自噬，从而影响疾病的进展。
- 序列相似性家族134成员B /
- 内质网自噬 /
- 选择性自噬 /
- 疾病
Abstract: Autophagy has the ability to degrade damaged senescent organelles and abnormal proteins, providing energy and raw materials for life activities. Autophagy is mainly divided into four stages, including the formation of autophagic precursors, autophagosomes, autophagic lysosomes and the degradation of autophagic contents by lysosome hydrolase, which depends on the lysosomal degradation system. The endoplasmic reiculum (ER) is the largest organelle in eukaryotes, the site of protein synthesis and processing, and the storage site for calcium ions; protein folding errors and calcium ion imbalances lead to ER dysfunction and activate ER autophagy. Autophagy maintains cell homeostasis; selective and non-selective autophagy are two types of autophagy based on degraded substrate specificity. ER-phagy is a type of selective autophagy mediated by ER receptors. FAM134B is the first mammalian ER-phagy receptor to be identified, which mediates ER-phagy involved in the pathogenesis of all types of diseases. Family with sequence similarity 134, member B(FAM134B) induced the bending and fragmentation of the ER through the LC3 interaction domain and the reticular homologous domain, which facilitated transport to lysosomes and promoted the degradation of the ER. Moderate ER-phagy clears the damaged ER and restores ER homeostasis, whereas excessive ER-phagy induces apoptosis. In general, low levels of autophagy are beneficial for cell survival, whereas excessive autophagy or autophagy dysfunction under stress is detrimental. This paper introduces autophagy, ER structure and function, ER-phagy and how FAM134B mediates ER-phagy. By reviewing the relevant literatures, this paper explains the relationship between FAM134B-mediated ER-phagy and nervous system, digestive system, cardiovascular diseases and infectious diseases, and suggests that ER-phagy can be controlled by regulating the expression of FAM134B, thereby interfering with the progression of diseases.
- Family with sequence similarity 134, member B /
- Endoplasmic reticulum autophagy /
- Selective autophagy /
- Disease

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