2026-02-25 バージニア工科大学
＜関連情報＞
- https://news.vt.edu/articles/2026/02/research_fralinbiomed_zhenyanampk.html
- https://www.science.org/doi/10.1126/sciadv.aeb3338
Ampkα2T172の活性化は、骨格筋における運動パフォーマンスとエネルギー伝達を決定づける Ampk alpha2 T172 activation dictates exercise performance and energy transduction in skeletal muscle
Ryan N. Montalvo, Xiaolu Li, Gina M. Many, Tyler J. Sagendorf, […] , and Zhen Yan
Science Advances Published:25 Feb 2026
Abstract
Adenosine 5′-monophosphate–activated protein kinase (AMPK) is an energetic sensor for metabolic regulation and integration. Here, we used CRISPR-Cas9 to generate nonactivatable Ampkα knock-in (KI) mice with mutation of threonine-172 phosphorylation site to alanine (T172A), circumventing the limitations of previous genetic interventions that disrupt the protein stoichiometry. KI mice of Ampkα2, but not Ampkα1, demonstrated phenotypic changes with increased fat-to-lean mass, impaired endurance exercise capacity, and diminished mitochondrial maximal respiration and conductance in skeletal muscle. Integrated temporal multiomics analysis (proteomics/phosphoproteomics/metabolomics) in skeletal muscle at rest and during exercise establishes a pleiotropic yet imperative role of Ampkα2 T172 activation for glycolytic and oxidative metabolism, mitochondrial respiration, and contractile function. There is a substantial overlap of skeletal muscle proteomic changes in Ampkα2 T172A KI mice with that of patients with type 2 diabetes. Our findings suggest that Ampkα2 T172 activation is critical for exercise performance and energy transduction in skeletal muscle and may serve as a therapeutic target for type 2 diabetes.
