ATG8 对 TFEB 激活的非经典作用。

Non-canonical roles of ATG8 for TFEB activation.

机构信息

Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan.

Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.

出版信息

Biochem Soc Trans. 2022 Feb 28;50(1):47-54. doi: 10.1042/BST20210813.

DOI:10.1042/BST20210813

PMID:35166325

Abstract

Autophagy is an evolutionally conserved cytoplasmic degradation pathway in which the double membrane structure, autophagosome sequesters cytoplasmic material and delivers them to lysosomes for degradation. Many autophagy related (ATG) proteins participate in the regulation of the several steps of autophagic process. Among ATGs, ubiquitin-like protein, ATG8 plays a pivotal role in autophagy. ATG8 is directly conjugated on lipid in autophagosome membrane upon induction of autophagy thus providing a good marker to monitor and analyze autophagy process. However, recent discoveries suggest that ATG8 has autophagy independent non-canonical functions and ATG8 positive structures are not always autophagosomes. This review briefly overviews canonical and non-canonical roles of ATG8 and introduce novel function of ATG8 to activate Transcriptional Factor EB(TFEB), a master transcription factor of autophagy and lysosome function during lysosomal damage.

摘要

自噬是一种进化上保守的细胞质降解途径，其中双层膜结构自噬体隔离细胞质物质，并将其递送至溶酶体进行降解。许多自噬相关（ATG）蛋白参与自噬过程的几个步骤的调节。在 ATG 中，泛素样蛋白 ATG8 在自噬的诱导中直接连接到自噬体膜上的脂质上，因此提供了一个很好的标记来监测和分析自噬过程。然而，最近的发现表明 ATG8 具有自噬独立的非典型功能，并且 ATG8 阳性结构并不总是自噬体。本综述简要概述了 ATG8 的典型和非典型作用，并介绍了 ATG8 激活转录因子 EB（TFEB）的新功能，TFEB 是自噬和溶酶体功能的主要转录因子，在溶酶体损伤时激活。