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The mechanism by which nutrient status regulates the fusion ofautophagosomes with endosomes/lysosomes is poorly understood.Here we showed that during C.elegans development,loss of function of O-linked-N-acetylglucosamine (O-GlcNAc)transferase(ogt-1) promotes autophagy activity.In mammalian cells,OGT knockdown elevates autophagic flux by promoting autophagosome formation and maturation.OGT knockdown facilitates autophagosome maturation byO-GlcNAcylation of SNAP-29 at Ser2,Ser61,Thr130 and Ser153.O-GlcNAcylation of SNAP-29 attenuates its interaction with Stx17 and VAMP8,which mediates fusion between autophagosomes and endosomes/lysosomes.Mutating the O-G1eNAc sites in SNAP-29 promotes formation of the SNAP-29-containing SNARE complex and increases autophagic flux.C.elegans SNAP-29 is O-GlcNAcylated at Ser70,Ser134,Thr143 and Ser249.O-GlcNAc modification-defective SNAP-29 facilitates autophagic degradation of protein aggregates in C.elegans.O-GleNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C.elegans.Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation.