Golgi-Associated ATG8ylation: Mechanisms and Biological Implications

ATG8ylation, the covalent conjugation of LC3/GABARAP-family proteins to lipids or proteins, is no longer viewed solely as a signature of canonical degradative autophagy. A rapidly growing literature has revealed that ATG8 conjugation also occurs on pre-existing single membranes through noncanonical autophagy, a process also referred to as conjugation of ATG8 to single membranes (CASM). The Golgi apparatus has emerged as a particularly important and conceptually revealing platform for this biological process. Recent studies have established that Golgi-associated ATG8ylation is not a passive by-product of organelle disruption, but a regulated response that can be initiated at the Golgi, often depends on the V-ATPase-ATG16L1 machinery, promotes stress-responsive transcriptional programs involving TFE3 and TFEB, mediates unconventional secretion of IL1β, and supports the repair of damaged Golgi architecture. Here, we synthesize these advances into a unified model in which Golgi-associated ATG8ylation functions as a membrane stress-response hub. In this model, Golgi perturbations are sensed through local changes in organelle state, including trafficking blockade, pH/ion imbalance, V-ATPase assembly, and cytoskeletal or ribbon disruption. These signals recruit or activate ATG8 conjugation machinery on Golgi membranes and generate functional outputs: membrane remodeling, Golgi repair, transcriptional stress adaptation, and unconventional secretion. We also discuss unresolved questions concerning membrane specificity, lipid acceptors, the distinction between repair and degradation, and the physiological roles of this pathway.