Endomembrane damage elicits homeostatic responses including ESCRT-dependent membrane repair and autophagic removal of damaged organelles. Previous studies have suggested that these systems may act separately. Here, we show that galectin-3 (Gal3), a β-galactoside-binding cytosolic lectin, unifies and coordinates ESCRT and autophagy responses to lysosomal damage. Gal3 and its capacity to recognize damage-exposed glycans were required for efficient recruitment of the ESCRT component ALIX during lysosomal damage. Both Gal3 and ALIX were required for restoration of lysosomal function. Gal3 promoted interactions between ALIX and the downstream ESCRT-III effector CHMP4 during lysosomal repair. At later time points following lysosomal injury, Gal3 controlled autophagic responses. When this failed, as in Gal3 knockout cells, lysosomal replacement program took over through TFEB. Manifestations of this staged response, which includes membrane repair, removal, and replacement, were detected in model systems of lysosomal damage inflicted by proteopathic tau and during phagosome parasitism by Mycobacterium tuberculosis.

中文翻译：

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Galectin-3协调溶酶体修复和去除的细胞系统。

膜内损伤引起体内稳态反应，包括ESCRT依赖性膜修复和自噬去除受损细胞器。先前的研究表明，这些系统可能单独起作用。在这里，我们表明，galectin-3（Gal3），一种β-半乳糖苷结合细胞溶质凝集素，统一并协调了ESCRT和自噬反应对溶酶体的损害。为了在溶酶体损伤期间有效募集ESCRT组分ALIX，需要Gal3及其识别暴露于损伤的聚糖的能力。恢复溶酶体功能需要Gal3和ALIX。在溶酶体修复过程中，Gal3促进了ALIX与下游ESCRT-III效应子CHMP4之间的相互作用。在溶酶体损伤后的较晚时间点，Gal3控制自噬反应。当失败时，例如在Gal3基因敲除细胞中，溶酶体替代计划通过TFEB接管。该阶段性反应的表现包括膜修复，去除和置换，是在由蛋白性tau造成的溶酶体损害模型系统中以及在结核分枝杆菌的吞噬体寄生过程中检测到的。