Human glycogenins maintain glucose homeostasis by regulating glycogen metabolism
Tzu-Han Weng,
Yu-Chung Pien,
Ching-Jou Chen,
Po-Pang Chen,
Yu-Ting Tseng,
Ying-Chen Chen,
Wen-Po Hsiao,
Ying-Ting Lee,
Yi-An Chen,
Yao-Chi Chen,
Carmay Lim,
Tzu-Han Hsu,
Sung-Jan Lin,
Hsin-Yung Yen,
Kuo-Chiang Hsia () and
Su-Yi Tsai ()
Additional contact information
Tzu-Han Weng: National Taiwan University
Yu-Chung Pien: National Taiwan University
Ching-Jou Chen: National Taiwan University
Po-Pang Chen: Academia Sinica
Yu-Ting Tseng: Academia Sinica
Ying-Chen Chen: National Taiwan University
Wen-Po Hsiao: National Taiwan University
Ying-Ting Lee: National Taiwan University
Yi-An Chen: Academia Sinica
Yao-Chi Chen: Academia Sinica
Carmay Lim: Academia Sinica
Tzu-Han Hsu: Academia Sinica
Sung-Jan Lin: National Taiwan University
Hsin-Yung Yen: Academia Sinica
Kuo-Chiang Hsia: Academia Sinica
Su-Yi Tsai: National Taiwan University
Nature Communications, 2025, vol. 16, issue 1, 1-21
Abstract:
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.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61862-3
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DOI: 10.1038/s41467-025-61862-3
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