ABSTRACT

Cellular stress response mechanisms typically increase organellar quantity and volume. To restore cellular homeostasis and organellar integrity, the surplus organelles are cleared by macroautophagy/autophagy, an intracellular process that shuttles cytoplasmic material to the lysosomes for degradation. The degradation is mediated by autophagy receptors that selectively link the degradable cargo to the autophagy machinery. Studies have identified receptors for the degradation of mitochondria, endoplasmic reticulum, lysosomes, and peroxisomes. The autophagic degradation of the Golgi, named Golgiphagy, however, has remained undefined. The Golgi is essential for the processing, sorting and trafficking of proteins and lipids in the secretory pathway. In a recent study, we identified CALCOCO1 as a Golgiphagy receptor in response to nutrient deprivation. CALCOCO1 interacts with Golgi membranes by binding to cytoplasmic Ankyrin repeat (AR) domains of Golgi resident ZDHHC17 and ZDHHC13 palmitoyltransferases (PATs) via a defined zDHHC-AR-binding motif (zDABM) to recruit autophagy machinery. Lack of CALCOCO1 in cells causes an impaired Golgiphagy and expansion of the Golgi.

摘要

细胞应激反应机制通常会增加细胞器的数量和体积。为了恢复细胞稳态和细胞器的完整性，多余的细胞器被巨自噬/自噬清除，这是一种将细胞质物质运送到溶酶体进行降解的细胞内过程。降解是由自噬受体介导的，该受体选择性地将可降解的货物与自噬机制连接起来。研究已经确定了线粒体、内质网、溶酶体和过氧化物酶体降解的受体。然而，被称为高尔基体的高尔基体自噬降解仍未确定。高尔基体对于分泌途径中蛋白质和脂质的加工、分类和运输至关重要。在最近的一项研究中，我们将 CALCOCO1 鉴定为响应营养剥夺的高尔基体受体。CALCOCO1 通过定义的 zDHHC-AR 结合基序 (zDABM) 与高尔基体 ZDHHC17 和 ZDHHC13 棕榈酰转移酶 (PAT) 的细胞质锚蛋白重复 (AR) 结构域结合，从而与高尔基体膜相互作用，以募集自噬机制。细胞中缺乏 CALCOCO1 会导致高尔基体吞噬功能受损和高尔基体扩张。