GORASP2 promotes phagophore closure and autophagosome maturation into autolysosomes

As the central hub of the secretory pathway, the Golgi apparatus plays a crucial role in maintaining cellular homeostasis in response to stresses. Recent studies have revealed the involvement of the Golgi tether, GORASP2, in facilitating autophagosome-lysosome fusion by connecting LC3-II and LAMP2 during nutrient starvation. However, the precise mechanism remains elusive. In this study, utilizing super-resolution microscopy, we observed GORASP2 localization on the surface of autophagosomes during glucose starvation. Depletion of GORASP2 hindered phagophore closure by regulating the association between VPS4A and the ESCRT-III component, CHMP2A. Furthermore, we found that GORASP2 controls RAB7A activity by modulating its GEF complex, MON1A-CCZ1, thereby impacting RAB7A's interaction with the HOPS complex. The assembly of both STX17-SNAP29-VAMP8 and YKT6-SNAP29-STX7 SNARE complexes was also attenuated without GORASP2. These findings suggest that GORASP2 helps seal autophagosomes and activate the RAB7A-HOPS-SNAREs membrane fusion machinery for autophagosome maturation, highlighting its membrane tethering function in response to stresses.