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巨自噬、微自噬和伴侣介导的自噬的分子机制。

Molecular Mechanisms of Macroautophagy, Microautophagy, and Chaperone-Mediated Autophagy.

机构信息

Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School.

出版信息

J Nippon Med Sch. 2024 Mar 9;91(1):2-9. doi: 10.1272/jnms.JNMS.2024_91-102. Epub 2023 Jun 2.

Abstract

Autophagy is a self-digestive process that is conserved in eukaryotic cells and responsible for maintaining cellular homeostasis through proteolysis. By this process, cells break down their own components in lysosomes. Autophagy can be classified into three categories: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Macroautophagy involves membrane elongation and microautophagy involves membrane internalization, and both pathways undergo selective or non-selective processes that transport cytoplasmic components into lysosomes to be degraded. CMA, however, involves selective incorporation of cytosolic materials into lysosomes without membrane deformation. All three categories of autophagy have attracted much attention due to their involvement in various biological phenomena and their relevance to human diseases, such as neurodegenerative diseases and cancer. Clarification of the molecular mechanisms behind these processes is key to understanding autophagy and recent studies have made major progress in this regard, especially for the mechanisms of initiation and membrane elongation in macroautophagy and substrate recognition in microautophagy and CMA. Furthermore, it is becoming evident that the three categories of autophagy are related to each other despite their implementation by different sets of proteins and the involvement of completely different membrane dynamics. In this review, recent progress in macroautophagy, microautophagy, and CMA are summarized.

摘要

自噬是一种在真核细胞中保守的自我消化过程,通过蛋白水解负责维持细胞内稳态。通过这个过程,细胞在溶酶体中分解自身的成分。自噬可以分为三种类型:巨自噬、微自噬和伴侣介导的自噬(CMA)。巨自噬涉及膜的伸长,微自噬涉及膜的内化,这两种途径都经历了选择性或非选择性的过程,将细胞质成分运输到溶酶体中进行降解。然而,CMA 涉及到细胞质物质的选择性掺入到溶酶体中,而不涉及膜的变形。由于自噬参与了各种生物学现象及其与人类疾病的相关性,如神经退行性疾病和癌症,因此所有三种类型的自噬都引起了广泛关注。阐明这些过程背后的分子机制是理解自噬的关键,最近的研究在这方面取得了重大进展,特别是在巨自噬的起始和膜伸长机制以及微自噬和 CMA 的底物识别方面。此外,尽管自噬的实施涉及不同的蛋白质组和完全不同的膜动力学,但三种类型的自噬之间存在关联,这一点变得越来越明显。在这篇综述中,总结了巨自噬、微自噬和 CMA 的最新进展。

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