Department of Chemistry, Umeå University, Umeå Centre for Microbial Research, Umeå, SE-90187, Sweden.
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
Chembiochem. 2023 Dec 14;24(24):e202300579. doi: 10.1002/cbic.202300579. Epub 2023 Nov 7.
Lipidation of the LC3 protein has frequently been employed as a marker of autophagy. However, LC3-lipidation is also triggered by stimuli not related to canonical autophagy. Therefore, characterization of the driving parameters for LC3 lipidation is crucial to understanding the biological roles of LC3. We identified a pseudo-natural product, termed Inducin, that increases LC3 lipidation independently of canonical autophagy, impairs lysosomal function and rapidly recruits Galectin 3 to lysosomes. Inducin treatment promotes Endosomal Sorting Complex Required for Transport (ESCRT)-dependent membrane repair and transcription factor EB (TFEB)-dependent lysosome biogenesis ultimately leading to cell death.
LC3 蛋白的脂质化通常被用作自噬的标志物。然而，LC3 的脂质化也会被与经典自噬无关的刺激触发。因此，描述 LC3 脂质化的驱动参数对于理解 LC3 的生物学功能至关重要。我们鉴定了一种假天然产物，称为诱导剂，它可以独立于经典自噬增加 LC3 的脂质化，损害溶酶体功能，并迅速将半乳糖凝集素 3 募集到溶酶体。诱导剂处理促进内体分选复合物必需的运输 (ESCRT)-依赖性膜修复和转录因子 EB (TFEB)-依赖性溶酶体生物发生，最终导致细胞死亡。
