Ampk alpha2 T172 activation dictates exercise performance and energy transduction in skeletal muscle.

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 activat

SUBMITTER: Montalvo RN 

PROVIDER: S-EPMC12935046 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature