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降解的随机过程:细胞的自噬溶酶体系统

Stochastics of Degradation: The Autophagic-Lysosomal System of the Cell.

作者信息

Kudriaeva A A, Sokolov A V, Belogurov A A Jr

机构信息

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997 Russia.

Lomonosov Moscow State University, Moscow, 119991 Russia.

出版信息

Acta Naturae. 2020 Jan-Mar;12(1):18-32. doi: 10.32607/actanaturae.10936.

Abstract

Autophagy is a conservative and evolutionarily ancient process that enables the transfer of various cellular compounds, organelles, and potentially dangerous cellular components to the lysosome for their degradation. This process is crucial for the recycling of energy and substrates, which are required for cellular biosynthesis. Autophagy not only plays a major role in the survival of cells under stress conditions, but is also actively involved in maintaining cellular homeostasis. It has multiple effects on the immune system and cellular remodeling during organism development. The effectiveness of autophagy is ensured by a controlled interaction between two organelles - the autophagosome and the lysosome. Despite significant progress in the description of the molecular mechanisms underlying autophagic-lysosomal system (ALS) functioning, many fundamental questions remain. Namely, the specialized functions of lysosomes and the role of ALS in the pathogenesis of human diseases are still enigmatic. Understanding of the mechanisms that are triggered at all stages of autophagic- lysosomal degradation, from the initiation of autophagy to the terminal stage of substrate destruction in the lysosome, may result in new approaches that could help better uderstand ALS and, therefore, selectively control cellular proteostasis.

摘要

自噬是一个保守且进化上古老的过程,它能将各种细胞化合物、细胞器以及潜在危险的细胞成分转运至溶酶体进行降解。这一过程对于细胞生物合成所需的能量和底物的循环利用至关重要。自噬不仅在应激条件下细胞的存活中起主要作用,还积极参与维持细胞内稳态。它在生物体发育过程中对免疫系统和细胞重塑具有多种影响。自噬体与溶酶体这两种细胞器之间的可控相互作用确保了自噬的有效性。尽管在描述自噬 - 溶酶体系统(ALS)功能的分子机制方面取得了重大进展,但许多基本问题仍然存在。具体而言,溶酶体的特殊功能以及ALS在人类疾病发病机制中的作用仍然是个谜。了解自噬 - 溶酶体降解各个阶段所触发的机制,从自噬的启动到溶酶体中底物破坏的终末阶段,可能会带来有助于更好理解ALS从而选择性控制细胞蛋白质稳态的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6675/7245954/f0f2c0b57a5f/AN20758251-12-01-018-g001.jpg

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