Lipidated ATG8/LC3 proteins are recruited to single membrane compartments as well as autophagosomes, supporting their functions. Although recent studies have shown that Golgi-LC3 lipidation follows Golgi damage, its molecular mechanism and function under Golgi stress remain unknown. Here, by combining DLK1 overexpression as a new strategy for induction of Golgi-specific LC3 lipidation, and the application of Golgi-damaging reagents, we unravel the mechanism and role of Golgi-LC3 lipidation. Upon DLK1 overexpression, LC3 is lipidated on the Golgi apparatus in an ATG12-ATG5-ATG16L1 complex-dependent manner; a post-Golgi trafficking blockade is the primary cause of this lipidation. During Golgi stress, ATG16L1 is recruited through its interaction with V-ATPase for Golgi-LC3 lipidation. After post-Golgi trafficking inhibition, TFE3, a key regulator of the Golgi stress response, is translocated to the nucleus. Defects in LC3 lipidation disrupt this translocation, leading to an attenuation of the Golgi stress response. Together, our results reveal the mechanism and unexplored function of Golgi-LC3 lipidation in the Golgi stress response.

中文翻译：

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非自噬性高尔基体-LC3 脂质化促进针对高尔基体功能障碍的 TFE3 应激反应。


脂质化的 ATG8/LC3 蛋白被募集到单膜区室和自噬体中，支持其功能。尽管最近的研究表明，高尔基体-LC3 脂质化发生在高尔基体损伤之后，但其在高尔基体胁迫下的分子机制和功能仍然未知。在这里，通过将 DLK1 过表达作为诱导高尔基体特异性 LC3 脂质化的新策略，以及高尔基体损伤试剂的应用，我们揭示了高尔基体-LC3 脂质化的机制和作用。DLK1 过表达后，LC3 以 ATG12-ATG5-ATG16L1 复合物依赖性方式在高尔基体上脂质化;高尔基体后贩运封锁是这种脂质化的主要原因。在高尔基体应激期间，ATG16L1通过与 V-ATP 酶的相互作用被募集以进行高尔基体-LC3 脂质化。在高尔基体后运输抑制后，TFE3（高尔基体应激反应的关键调节因子）易位到细胞核。LC3 脂质化缺陷破坏了这种易位，导致高尔基体应激反应减弱。总之，我们的结果揭示了高尔基体-LC3 脂质化在高尔基体应激反应中的机制和未探索的功能。