Autophagy is essential for maintaining cellular homeostasis and survival under various stress conditions. Autophagy-related gene 9 (Atg9) encodes a multipass transmembrane protein thought to act as a membrane carrier for forming autophagosomes. However, the molecular regulation and physiological importance of Atg9 in animal development remain largely unclear. Here, we generated Atg9 null mutant flies and found that loss of Atg9 led to shortened lifespan, locomotor defects, and increased susceptibility to stress. Atg9 loss also resulted in aberrant adult midgut morphology with dramatically enlarged enterocytes. Interestingly, inhibiting the TOR signaling pathway rescued the midgut defects of the Atg9 mutants. In addition, Atg9 interacted with PALS1-associated tight junction protein (Patj), which associates with TSC2 to regulate TOR activity. Depletion of Atg9 caused a marked decrease in TSC2 levels. Our findings revealed an antagonistic relationship between Atg9 and TOR signaling in the regulation of cell growth and tissue homeostasis.

中文翻译：

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Atg9 拮抗 TOR 信号调节果蝇肠细胞生长和上皮稳态

自噬对于在各种压力条件下维持细胞稳态和存活至关重要。自噬相关基因 9 (Atg9) 编码一种多通道跨膜蛋白，被认为是形成自噬体的膜载体。然而，Atg9 在动物发育中的分子调控和生理重要性仍不清楚。在这里，我们生成了 Atg9 空突变果蝇，发现 Atg9 的缺失导致寿命缩短、运动缺陷和对压力的敏感性增加。Atg9 缺失还导致成人中肠形态异常，肠细胞显着增大。有趣的是，抑制 TOR 信号通路可以挽救 Atg9 突变体的中肠缺陷。此外，Atg9 与 PALS1 相关的紧密连接蛋白 (Patj) 相互作用，后者与 TSC2 相关联以调节 TOR 活性。Atg9 的消耗导致 TSC2 水平显着降低。我们的研究结果揭示了 Atg9 和 TOR 信号在调节细胞生长和组织稳态方面的拮抗关系。