Noda Takeshi
Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
Biomolecules. 2017 Jul 7;7(3):52. doi: 10.3390/biom7030052.
Autophagy is an intracellular protein-degradation process that is conserved across eukaryotes including yeast and humans. Under nutrient starvation conditions, intracellular proteins are transported to lysosomes and vacuoles via membranous structures known as autophagosomes, and are degraded. The various steps of autophagy are regulated by the target of rapamycin complex 1 (TORC1/mTORC1). In this review, a history of this regulation and recent advances in such regulation both in yeast and mammals will be discussed. Recently, the mechanism of autophagy initiation in yeast has been deduced. The autophagy-related gene 13 (Atg13) and the unc-51 like autophagy activating kinase 1 (Ulk1) are the most crucial substrates of TORC1 in autophagy, and by its dephosphorylation, autophagosome formation is initiated. Phosphorylation/dephosphorylation of Atg13 is regulated spatially inside the cell. Another TORC1-dependent regulation lies in the expression of autophagy genes and vacuolar/lysosomal hydrolases. Several transcriptional and post-transcriptional regulations are controlled by TORC1, which affects autophagy activity in yeast and mammals.
自噬是一种细胞内蛋白质降解过程，在包括酵母和人类在内的真核生物中保守存在。在营养饥饿条件下，细胞内蛋白质通过称为自噬体的膜结构被运输到溶酶体和液泡中并被降解。自噬的各个步骤由雷帕霉素复合物1（TORC1/mTORC1）的靶点调控。在本综述中，将讨论这种调控的历史以及酵母和哺乳动物中这种调控的最新进展。最近，酵母中自噬起始的机制已被推导出来。自噬相关基因13（Atg13）和unc-51样自噬激活激酶1（Ulk1）是自噬中TORC1最重要的底物，通过其去磷酸化，启动自噬体形成。Atg13的磷酸化/去磷酸化在细胞内空间上受到调控。另一种TORC1依赖性调控在于自噬基因和液泡/溶酶体水解酶的表达。TORC1控制着几种转录和转录后调控，这影响了酵母和哺乳动物中的自噬活性。
