Résumé
AMP-activated protein kinase (AMPK) is a critical enzyme in conditions of cellular energy deficit such asexercise, hypoxia or nutritional stress. AMPK is well known to regulate protein degradation pathwaysnotably through FOXO-related axis. In this study, we investigated the implication of AMPK activation inFOXO3 expression and stability in skeletal muscle primary myotubes. First, time course and doseresponse studies revealed optimal AICAR treatment duration and dose in skeletal muscle cells. Then,experiments with cycloheximide treatment of primary myotubes highlighted that AICAR infusion ex-tends FOXO3 protein half-life. Our results also showed that AICAR treatment or nutrient depletion in-creases FOXO3 expression in primary myotubes and the expression of the mitochondrial E3 ligase Mul1involved in mitochondrial turnover (mitophagy). In AMPK KO cells, nutrient depletion failed to alter thelevel of some FOXO3-dependent atrophic genes, including LC3B, BNIP3, and the mitochondrial E3 ligaseMul1, but not the expression of other genes (i.e.FOXO1, Gabarapl1, MAFbx, MuRF1). In summary, our datahighlight that AMPK stabilizes FOXO3 and suggest a role in the first initiation step of mitochondrialsegregation in muscle cells.