| First Author | Jiang P | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 3 | Pages | 629-637.e5 |
| PubMed ID | 33400924 | Mgi Jnum | J:305185 |
| Mgi Id | MGI:6510348 | Doi | 10.1016/j.molcel.2020.12.008 |
| Citation | Jiang P, et al. (2021) Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53. Mol Cell 81(3):629-637.e5 |
| abstractText | As a master regulator of metabolism, AMP-activated protein kinase (AMPK) is activated upon energy and glucose shortage but suppressed upon overnutrition. Exaggerated negative regulation of AMPK signaling by nutrient overload plays a crucial role in metabolic diseases. However, the mechanism underlying the negative regulation is poorly understood. Here, we demonstrate that high glucose represses AMPK signaling via MG53 (also called TRIM72) E3-ubiquitin-ligase-mediated AMPKalpha degradation and deactivation. Specifically, high-glucose-stimulated reactive oxygen species (ROS) signals AKT to phosphorylate AMPKalpha at S485/491, which facilitates the recruitment of MG53 and the subsequent ubiquitination and degradation of AMPKalpha. In addition, high glucose deactivates AMPK by ROS-dependent suppression of phosphorylation of AMPKalpha at T172. These findings not only delineate the mechanism underlying the impairment of AMPK signaling in overnutrition-related diseases but also highlight the significance of keeping the yin-yang balance of AMPK signaling in the maintenance of metabolic homeostasis. |
