The Golgi stacking protein GORASP2/GRASP55 serves as an energy sensor to promote autophagosome maturation under glucose starvation.

The Golgi apparatus is a central intracellular membrane organelle in the secretory pathway. The formation of the unique stacked architecture of the Golgi ensures accurate protein glycosylation and sorting. However, how the Golgi structure and function respond to extracellular stresses is largely unexplored. In a recent study, we reported that under short-term glucose deprivation, a subpopulation of the Golgi stacking protein GORASP2/GRASP55 is targeted from the Golgi to the interface between autophagosomes and lysosomes to promote autophagosome maturation; this process is regulated by O-GlcNAcylation. Under growth condition, GORASP2 is O-GlcNAcylated and functions as a stacking protein in the Golgi. Upon glucose starvation, GORASP2 is de-O-GlcNAcylated and is partially relocated from the Golgi to the autophagosome-lysosome interface, where it interacts with lipidated LC3 on autophagosomes and LAMP2 on lysosomes, and functions as a membrane tether to facilitate autophagosome-lysosome fusion. Therefore, our study uncovered an unconventional role of the Golgi 'glue' protein in autophagy that acts by sensing the glucose level.