Fig. 7: Structural evolution of STBD1 distinguishes glycophagy between oysters and vertebrates.

STBD1-mediated glycophagy originated before the diversification of bilaterians. In mollusks and other lophotrochozoans, STBD1α represents the ancestral domain architecture of STBD1 proteins. Among them, oyster STBD1α binds glycogen with high affinity and subsequently anchors to GABARAPL2, facilitating glycophagic flux and providing a primary energy source. Vertebrate STBD1β proteins inherited an ancestral chordate rearrangement of the CBM20 domain to the C-terminus, resulting in lower binding affinity with glycogen compared to the N-terminal position, leading to a relatively reduced glycophagic flux through the glycophagy pathway by binding with GABARAPL or GABARAPL1. Consequently, oysters utilize glycophagy to degrade glycogen as a primary energy source, whereas vertebrates rely more strongly on lipophagy. LD lipid droplet, FFA free fat acid. Created in BioRender. Ren, L. (2025) https://BioRender.com/u86c722. Parts of this figure were created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license. The silhouette images of the animals in this figure were modified from PhyloPic (https://www.phylopic.org/), which is an open database of free silhouette images of animals, plants, and other life forms, available for reuse under Creative Commons licenses.