Autophagy mediates the degradation of harmful material within lysosomes. In aggrephagy, the pathway mediating the degradation of aggregated, ubiquitinated proteins, this cargo material is collected in larger condensates prior to its sequestration by autophagosomes. In this process, the autophagic cargo receptors SQSTM1/p62 and NBR1 drive cargo condensation, while TAX1BP1, which binds to NBR1, recruits the autophagy machinery to facilitate autophagosome biogenesis at the condensates. The mechanistic basis for the TAX1BP1-mediated switch from cargo collection to its sequestration is unclear. Here we show that TAX1BP1 is not a constitutive component of the condensates. Its recruitment correlates with the induction of autophagosome biogenesis. TAX1BP1 is sufficient to recruit the TBK1 kinase via the SINTBAD adapter. We define the NBR1-TAX1BP1-binding site, which is adjacent to the GABARAP/LC3 interaction site, and demonstrate that the recruitment of TAX1BP1 to cargo mimetics can be enhanced by an increased ubiquitin load. Our study suggests that autophagosome biogenesis is initiated once sufficient cargo is collected in the condensates.

中文翻译：

---

自噬起始剂的募集TAX1BP1将聚集性从货物收集推进到封存。


自噬介导溶酶体内有害物质的降解。在聚集自噬中，介导聚集的泛素化蛋白质降解的途径，这种货物物质在被自噬体隔离之前被收集在较大的凝聚物中。在这个过程中，自噬货物受体 SQSTM1/p62 和 NBR1 驱动货物凝聚，而与 NBR1 结合的 TAX1BP1 募集自噬机制以促进自噬体在凝聚物处的生物发生。TAX1BP1介导的从货物收集转向封存的机制基础尚不清楚。在这里，我们表明 TAX1BP1 不是凝聚态的组成成分。它的募集与自噬体生物发生的诱导相关。TAX1BP1 就足以通过 SINTBAD 接头募集 TBK1 激酶。我们定义了与 GABARAP/LC3 相互作用位点相邻的 NBR1-TAX1BP1 结合位点，并证明TAX1BP1向货物模拟物的募集可以通过增加泛素载量来增强。我们的研究表明，一旦在冷凝物中收集了足够的货物，自噬体生物发生就会启动。