在外界各种刺激时，细胞会通过改变自身的状态，如诱导自噬等方式来适应外界环境的变化，这些变化对于维持细胞稳态具有非常关键的作用。自噬体-溶酶体动态互作对于自噬功能的正常行使是极其重要的。但是目前对于其互作的调控机制所知甚少。我们的研究发现：WDRDSB正向调控自噬体-溶酶体互作，而SPSA1负向调控自噬体溶酶体互作。此外，我们发现mTOR可能通过磷酸化修饰WDRDSB负向调控自噬SNARE复合体的形成，抑制自噬体-溶酶体的互作。但对于WDRDSB和SPSA1如何协作调控自噬体溶酶体互作的精细机制还不清楚。因此，申请人拟采用细胞生物学、分子生物学等手段和技术结合体外重建系统，深入研究应激条件下mTOR通过控WDRDSB和SPSA1调节自噬体-溶酶体互作的分子机制。本研究的顺利进展将揭示新的自噬体-溶酶体互作机制，将为应激条件下细胞器动态互作的多样性、复杂性和和高效性提供一个更深入全面的认识。

Autophagy is induced to maintain homeostasis when cells are subjected to various stimuli. Autophagosomes fuse with lysosomes is extremely important for autophagy. However, little is known about the mechanism of this fusion process. Our preliminary data showed that WDRDSB promotes autophagosome-lysosome fusion, while SPSA1 blocks autophagosome -lysosome fusion. In addition, we also found WDRDSB is phosphorylated by mTOR. The phosphorylation of WDRDSB inhibits the formation of autophagic SNARE complexes and autophagosome-lysosome fusion. However, it is unclear how the WDRDSB and SPSA1 cooperate to regulate autophagosome- lysosome fusion. The applicant intends to combine the technology of molecular biology, cell biology and in vitro reconstitution to further investigate the molecular mechanism of how WDRDSB and SPSA1 regulate autophagosome-lysosome fusion and its upstream signaling pathway. This study would provide a more diverse and comprehensive understanding of autophagosome-lysosome fusion.