Glycophagy is an ancient bilaterian pathway supporting metabolic adaptation through STBD1 structural evolution

Area of Science:

• Cell Biology
• Evolutionary Biology
• Biochemistry

Background:

• Glycophagy is a selective autophagy pathway essential for glycogen homeostasis.
• Starch-binding domain-containing protein 1 (STBD1) acts as the cargo receptor for glycophagy.
• The evolutionary history and structural variations of STBD1 are not well understood.

Purpose of the Study:

• To investigate the evolutionary origins and functional significance of STBD1 in glycophagy.
• To explore the role of glycophagy in glycogen metabolism in the Pacific oyster, Crassostrea gigas.
• To understand how structural differences in STBD1 impact glycogen binding and autophagosome targeting.

Main Methods:

• Phylogenetic and comparative genomic analysis of the CBM20 domain in STBD1 across metazoans.
• Identification and characterization of STBD1 in the Pacific oyster.
• Structural modeling and functional assays to assess glycogen binding and protein interactions.

Main Results:

• The Pacific oyster utilizes glycophagy for glycogen mobilization during energy deprivation.
• Oyster STBD1 possesses an N-terminal CBM20 domain, common in invertebrates, contrasting with vertebrate STBD1's C-terminal CBM20.
• N-terminal CBM20 organization enhances glycogen binding and facilitates autophagosome engulfment, indicating deep conservation of glycophagy in bilaterians.

Conclusions:

• Glycophagy is an ancient and deeply conserved metabolic process in bilaterian animals.
• The structural evolution of STBD1, particularly the location of its CBM20 domain, has contributed to adaptive variations in metabolic strategies across animal lineages.
• STBD1's N-terminal CBM20 domain plays a crucial role in efficient glycogen management via glycophagy.