Figure 2.

Membrane damage repair and removal. The endosome is constantly challenged by pathogens (bacteria, virus, and fungi), protein aggregates, or chemicals that can disrupt its membrane and provoke injuries of different sizes. Small disruptions (<100 nm) trigger a leakage of Ca²⁺ into the cytoplasm and activate LRKK2. LRKK2 and Ca²⁺ effectors mediate the recruitment of the ESCRT machinery to promote repair of the injured organelle. Galectin-3 (Gal3) is recruited to damage sites and may promote ESCRT assembly. If the injury is too large, the cell will trigger a process of degradation called lysophagy. During lysophagy, damaged vacuoles are sensed and tagged by galectins (Gal) and ubiquitin (Ub). Both signals mediate the recruitment of the autophagic machinery (either directly via autophagic receptors, such as the sequestosome like receptors (SLRs) or indirectly via TRIMs). The membrane remnant is engulfed in a double-membrane vesicle called autophagosome, which fuses with lysosomes for content degradation and recycling. Autophagy is also controlled by metabolic kinase mechanistic target of rapamycin (mTOR) through Gal8. Moreover, Gal9 can also control autophagy induction by directly activating AMP-activated protein kinase (AMPK) in response to endosomal damage to inhibit mTOR. See text for details. Abbreviations: ESCRT, endosomal sorting complexes required for transport; Gal8, galectin8; LRRK2, Leucine-rich repeat kinase 2; ROS, reactive oxygen species; Ub, ubiquitin.