Autophagy is controlled in part by the repression and activation of Autophagy-related (ATG) gene transcription. Here, we demonstrate that the conserved Cdk8 Kinase Module (CKM) of the mediator complex represses transcription of several ATG genes. To relieve this repression following nitrogen starvation, Med13 is rapidly degraded via a novel selective autophagy mechanism. This pathway requires the core autophagy machinery but is independent of known nucleophagy systems. It requires the cytosolic filament nucleoporin Gle1, the sorting nexin Snx4-Atg20 heterodimer, and the scaffold protein Atg17. This suggests a model where Med13 traverses through the nuclear pore complex, passing from Gle1 to Snx4. Snx4 then transports Med13 to autophagosomes by binding to Atg17. This previously unidentified nucleophagy pathway also mediates the autophagic degradation of two transcriptional activators of ATG genes (Rim15, Msn2) suggesting that this mechanism targets transcription factors that regulate ATG expression. This system provides a new level of selectivity, permitting the cell to fine-tune the autophagic response by controlling the turnover of both positive and negative ATG transcription factors.

中文翻译：

---

Snx4介导的噬核作用靶向控制ATG基因表达的转录因子

自噬部分受自噬相关（ATG）基因转录的阻遏和激活控制。在这里，我们证明了介导复合体的保守的Cdk8激酶模块（CKM）抑制了几个ATG基因的转录。为了缓解氮饥饿后的这种抑制，Med13通过新型选择性自噬机制迅速降解。该途径需要核心自噬机制，但独立于已知的核噬菌系统。它需要胞浆细丝核孔蛋白Gle1，分选nexin Snx4-Atg20异二聚体和支架蛋白Atg17。这表明Med13穿过Gle1到Snx4穿过核孔复合体。然后，Snx4通过与Atg17结合将Med13转运至自噬体。此先前未确定的核吞噬途径还介导了ATG基因的两个转录激活因子（Rim15，Msn2）的自噬降解，表明该机制靶向调节ATG表达的转录因子。该系统提供了新的选择性水平，允许细胞通过控制正和负ATG转录因子的更新来微调自噬反应。