| First Author | Zhou Q | Year | 2022 |
| Journal | Mol Cell | Volume | 82 |
| Issue | 24 | Pages | 4700-4711.e12 |
| PubMed ID | 36384136 | Mgi Jnum | J:332627 |
| Mgi Id | MGI:7424739 | Doi | 10.1016/j.molcel.2022.10.030 |
| Citation | Zhou Q, et al. (2022) Energy sensor AMPK gamma regulates translation via phosphatase PPP6C independent of AMPK alpha. Mol Cell 82(24):4700-4711.e12 |
| abstractText | Maintenance of energy level to drive movements and material exchange with the environment is a basic principle of life. AMP-activated protein kinase (AMPK) senses energy level and is a major regulator of cellular energy responses. The gamma subunit of AMPK senses elevated ratio of AMP to ATP and allosterically activates the alpha catalytic subunit to phosphorylate downstream effectors. Here, we report that knockout of AMPKgamma, but not AMPKalpha, suppressed phosphorylation of eukaryotic translation elongation factor 2 (eEF2) induced by energy starvation. We identified PPP6C as an AMPKgamma-regulated phosphatase of eEF2. AMP-bound AMPKgamma sequesters PPP6C, thereby blocking dephosphorylation of eEF2 and thus inhibiting translation elongation to preserve energy and to promote cell survival. Further phosphoproteomic analysis identified additional targets of PPP6C regulated by energy stress in an AMPKgamma-dependent manner. Thus, AMPKgamma senses cellular energy availability to regulate not only AMPKalpha kinase, but also PPP6C phosphatase and possibly other effectors. |
