细胞自噬通过降解脂肪和蛋白等能量物质而维持细胞存活，与动物的正常生长发育及肿瘤和癌症等疾病密切相关。申请者提早圆满完成了青年基金项目31101670预定任务，并发现下调家蚕脂肪体内的细胞自噬可导致幼虫变态发育异常、蛹重下降减少、成虫生殖能力下降。后续研究发现细胞自噬中断后，脂肪体中脂肪和储存蛋白的代谢受阻，基本证实了细胞自噬可动用脂肪体储存的能量物质而维持成虫器官形成和生殖发育这一假说。我们将利用家蚕和果蝇两种模式昆虫：（1）剖析细胞自噬介导脂肪降解的分子机制，为酸性脂肪酶参与细胞自噬和溶酶体介导的脂肪降解提供直接的细胞生物学证据；（2）阐释细胞自噬通过调控细胞内吞而影响储存蛋白代谢的作用机理，并提供一个解答细胞自噬和细胞内吞相互关系的研究体系。本项目有助于揭示细胞自噬通过影响脂肪体脂肪和储存蛋白代谢而调控昆虫变态和生殖发育的生命本质，并为高等动物相关研究提供重要借鉴，具有普遍生物学意义。

Via the degradation of stored lipids and proteins to maintain cell survival, autophagy plays critical roles in normal development and diseases such as tumor progression and cancer in animals. The applicant has successfully completed the previous Youth Fund Project 31101670 in advance, with five SCI papers including one publication in Autophagy. Meanwhile, we have discoverd that decreasing autophagy in the Bombyx fat body results in abnormal larval-pupal transition, pupal development and reproductive ability in adults. Later studies revealed that decreasing autophagy disrupted normal metabolism of the stored lipids and proteins in the Bombyx fat body, solidifying the hypothesis that autophagy mobilizes the stored energy resources in the larval fat body to maintain adult organ formation and reproductive maturation. On the basis of these findings, we aim to continuously unravel the detailed molecular mechanisms using Bombyx and Drosophila as two model insects. First, we will provide direct cellular evidences how acid lipases, lipid droplet, and lysosome participate in autophagy-mediated lipid degradation. Second, we will illustrate how autophagy affects endocytosis of the storage proteins to disrupt their normal metabolism, bringing up a unique in vivo system to dissect out the sophisticated relationship between autophagy and endocytosis. The accomplishment of this project will help illustrate the detailed molecular mechanisms how autophagy mobilizes the stored lipids and proteins in the larval fat body for supporting adult organ formation and reproductive maturation. This project will shed lights on general studies on autophagy-regulated metabloism and development in mammals.