AMP-Activated Protein Kinase (AMPK) at the Crossroads Between CO₂ Retention and Skeletal Muscle Dysfunction in...

Skeletal muscle dysfunction is a major comorbidity in chronic obstructive pulmonary disease (COPD) and other pulmonary conditions. Chronic CO₂ retention, or hypercapnia, also occur in some of these patients. Both muscle dysfunction and hypercapnia associate with higher mortality in these populations. Over the last years, we have established a mechanistic link between hypercapnia and skeletal muscle dysfunction, which is regulated by AMPK and causes depressed anabolism via reduced ribosomal biogenesis and accelerated catabolism via proteasomal degradation. In this review, we discuss the main findings linking AMPK with hypercapnic pulmonary disease both in the lungs and skeletal muscles, and also outline potential avenues for future research in the area based on knowledge gaps and opportunities to expand mechanistic research with translational implications.