细胞内的自噬可以被饥饿，细胞器损伤，病原体感染，低氧，热激等多种侵扰因素激活。但是我们对自噬过程是否及如何应对细胞机械损伤或支撑结构的破坏仍然知之甚少。在本项目中，我们选用秀丽线虫表皮上皮细胞层为研究模型，系统性地检测各类上皮细胞支撑结构(包括细胞骨架，细胞黏着结构和胞外基质层等)的损坏对自噬过程的调控作用。已完成的实验结果显示，绝大多数支撑结构的破坏均不会引起显著自噬现象，只有底膜黏着结构和基底膜胞外基质的缺失可明显激活自噬过程。相反，上皮细胞顶膜黏着结构的破坏可有效阻断热激引起的自噬小体形成。这些研究成果表明上皮细胞特定支撑结构对自噬的调控作用具有明显的空间特异性。我们计划深入解析上皮细胞不同支撑结构促进或抑制自噬的分子机制，并且探索这些调控机制对细胞存活和生理功能的影响。本课题的研究成果可以为各种与自噬或上皮细胞结构损伤相关的疾病的病理机制提供基础的理论支持。

A variety of cellular stresses, such as starvation, organelle damage, heat stress, hypoxia and pathogen infection can trigger the autophagic process. However, whether the autophagy machinery can be regulated by structural damage of the cell remains largely unknown. In this work, we utilize the C. elegans epidermis as the model and systemically investigate the relationship between damage of mechanical supporting structures (cytoskeletons, cell junctions, adhesions and extracellular matrix) and autophagy induction. Our results show that, surprisingly, most types of structural damage do not trigger autophagy. Only damage of basal extracellular matrix or the underlying muscle cells activates a distinct autophagic response in the epidermis. On the contrary, detachment of the epidermal cells from the apical extracellular matrix inhibits autophagosome formation caused by heat stress. Our discoveries reveal that the autophagic activation or inhibition in response to epidermal structural damage is clearly spatially restricted. We plan to explore in-depth the underlying mechanisms of how the epidermal supporting structures regulate autophagy, and how they may affect the survival and damage repair of the epidermal cells. The results obtained from these studies will not only help us better understand the pathogenesis of structural damage- and autophagy-related diseases, but also provide insight into more generic rules of autophagy regulation by the structural and mechanical properties of the cells across species.