期刊
GENES & DEVELOPMENT
卷 31, 期 16, 页码 1655-1665出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.305441.117
关键词
O-GlcNAcylation; glucagon; CaMKII; Ulk; autophagy; glucose production
资金
- National Institutes of Health (NIH) [R01DK089098, R01DK102648, CT DPH2014-0139]
- American Cancer Society
- Ellison Medical Foundation
- NIH [P01DK57751, P30DK34989]
- American Heart Association [14SDG20120052]
Starvation induces liver autophagy, which is thought to provide nutrients for use by other organs and thereby maintain whole-body homeostasis. Here we demonstrate that O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is required for glucagon-stimulated liver autophagy and metabolic adaptation to starvation. Genetic ablation of OGT in mouse livers reduces autophagic flux and the production of glucose and ketone bodies. Upon glucagon-induced calcium signaling, calcium/calmodulin-dependent kinase II (CaMKII) phosphorylates OGT, which in turn promotes O-GlcNAc modification and activation of Ulk proteins by potentiating AMPK-dependent phosphorylation. These findings uncover a signaling cascade by which starvation promotes autophagy through OGT phosphorylation and establish the importance of O-GlcNAc signaling in coupling liver autophagy to nutrient homeostasis.
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