Glycophagy: molecular mechanisms, regulatory signals, and disease associations

Glycophagy is a process of selective degradation of glycogen through the autophagy pathway. It relies on key proteins, such as STBD1 (glycogen-specific autophagy receptor), GABARAPL1 (member of the ATG8 family), and acid α-glucosidase (GAA), and proceeds through the steps of "glycogen recognition - autophagosome encapsulation - lysosomal degradation" to release glucose, thereby maintaining energy homeostasis. This process is regulated by multiple signaling pathways, such as AMPK, mTOR, CAMP/PKA, and calcium signaling pathways, which jointly respond to cellular energy demands and metabolic states. Glycophagy occurs under conditions, such as starvation, exercise, and energy metabolism disorders, and plays a role in diseases with glycogen metabolism disorders. Its functions include energy supply, blood sugar regulation, maintenance of cellular homeostasis, and influencing cellular aging. Dysfunction of glycophagy can lead to various diseases, such as glycogen storage diseases and diabetic cardiomyopathy. In-depth study of the regulatory mechanisms of glycophagy is helpful for developing therapeutic strategies for related diseases.