Human glycogenins maintain glucose homeostasis by regulating glycogen metabolism
Journal
Nature Communications
Journal Volume
16
Journal Issue
1
Start Page
Article number: 6556
ISSN
2041-1723
Date Issued
2025-07-16
Author(s)
Weng, Tzu-Han
Pien, Yu-Chung
Chen, Ching-Jou
Chen, Po-Pang
Tseng, Yu-Ting
Chen, Ying-Chen
Hsiao, Wen-Po
Lee, Ying-Ting
Chen, Yi-An
Chen, Yao-Chi
Lim, Carmay
Hsu, Tzu-Han
Yen, Hsin-Yung
Hsia, Kuo-Chiang
Abstract
Proper regulation of glycogen metabolism is fundamental to cellular energy homeostasis, and its disruption is associated with various metabolic disorders, including glycogen storage diseases (GSDs) and potentially diabetes. Despite glycogen’s role as an essential energy reservoir, the mechanisms governing its synthesis and structural diversity across tissues remain unclear. Here, we uncover the distinct physiological roles of the human glycogenins GYG1 and GYG2 in glycogen synthesis. Through cellular models, structural biology, and biochemical analyses, we demonstrate that, unlike GYG1, GYG2 exhibits minimal autoglycosylation activity and acts as a suppressor of glycogen formation. Together, these two glycogenins coordinate glycogen synthase activity and influence glycogen assembly in a cell-type-dependent manner. Importantly, these glycogenins modulate glucose metabolic pathways, thereby ensuring cellular glucose homeostasis. These findings address longstanding questions in glycogen metabolism and establish both GYG1 and GYG2 as critical regulators of glycogen synthesis and breakdown in human, providing insights with potential therapeutic implications for treating GSDs and metabolic diseases.
Publisher
Springer Science and Business Media LLC
Type
journal article