2022, Vol. 26 ›› Issue (20): 3243-3249

Role and regulatory mechanism of glycophagy in glycogen metabolism

Lyu Yuhu1, Cheng Lin1, Lin Wentao2, Peng Fenglin1   

Abstract: BACKGROUND: Glycophagy is a selective autophagy, which plays a unique role in glycogen degradation, but the mechanism of its regulation is still limited.
OBJECTIVE: To review the function and regulatory signaling pathway of glycophagy based on the morphology, function and degradation pathway of glycophagy substrate, and then to clarify the role and regulatory mechanism of glycophagy in glycogen metabolism.
METHODS: Web of Science, PubMed, and EBSCO databases were searched for the relevant English literatures using the search terms of glycophagy [Topic], Glycogen [Title] AND autophagy [Title], Glycogen-storage-disease [Title], Lafora-disease [Title], pompe-disease[Title], and Von-Gierke-disease [Title]. CNKI database was also searched to retrieve the relevant Chinese literatures with the search terms of glycogenated [Topic], glycogen autophagy [Title], glycogen accumulation [Title], and glycogen storage [Title]. Relevant literature was also manually retrieved. Based on the exclusion criteria, 87 papers were included for final review by reading the title and abstract.
RESULTS AND CONCLUSION: The glycogen degradation system in vivo consists of glycophagy and glycogen oxidative phosphorylation, which can provide substrates for the generation of glycolipids and fats, and prevent more serious events through storing a certain amount of glycogen in glycogenosomes during energy stress. However, glycophagy disorders can cause some diseases that are even life-threatening, such as Lafora disease, von Gierke disease and Pompe disease. The activation of PI3K/mTOR, Akt/FoxO and SGK1/mTOR signaling pathways could inhibit glycophagy, while glycophagy can be elicited through the activation of cAMP/PKA, G6PC/SIRT1/FoxO, Ca2+, cGMP/PKG/GSK-3β signaling pathways. However, There are many problems that need to be solved, such as: (1) whether there is sex difference during glycophagy; (2) what signals or stimuli lead to an increase in glycogen storage during glycophagy; (3) what substances trigger enzymes in lysosomes to degrade glycogen; (4) whether there is a balance point between glycogen degradation and storage during glycophagy; and (5) how the various regulatory pathways of glycophagy are coordinated, and what are the mechanisms of action and pharmacology.
Key words: glycophagy, glycogen autophagy, glycogen metabolism, autophagy, glycogen, signal pathway