A group from Tumour Cell Death and Autophagy Laboratory, Cancer Research UK Beatson Institute, Glasgow, UK, etc. has reported that glycan degradation promotes macroautophagy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245654/
Since macroautophagy is a major mechanism for the degradation of long-lived proteins and the only mechanism to degrade organelles described so far, perturbation of autophagy can lead to a variety of diseases, including neurodegenerative diseases, inflammatory diseases, diabetes, and cancer.
Due to the large proportion of proteins that are glycosylated, it was postulated that macroautophagy must be dependent not only on enzymes that degrade polypeptides, but also on those that degrade glycans.
Authors have found that glycan breakdown, specifically defucosylation, is a contributing step in the process of macroautophagy.
It was shown that loss of expression of the lysosomal glycosidase FUCA1 in cells and tissues causes accumulation of autophagosomes, indicating that FUCA1 modulates both basal and stimulated autophagy. Furthermore, it was shown that FUCA1 supports both autophagosome–lysosome fusion (loss of FUCA1 causes a stall in the fusion process) and the turnover stage of autophagy (loss of FUCA1 caused an increase in LC3-II levels under baseline conditions, but do not completely block, the turnover stage of the process). It is notable that under starvation conditions, it was found that FUCA1 loss decreases the rate of autophagosome clearance, as well as the degradation of mitochondria upon induction of mitophagy, indicating that FUCA1 is required for efficient autophagic flux in multiple contexts.
The importance of FUCA1 is exemplified by mutations in the gene, which lead to the congenital lysosomal storage disorder fucosidosis.