Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle

• Published in: Journal of applied physiology (1985) Vol. 118; no. 8; pp. 971 - 979
• Main Authors: Møller, Andreas Buch, Vendelbo, Mikkel Holm, Christensen, Britt, Clasen, Berthil Forrest, Bak, Ann Mosegaard, Jørgensen, Jens O L, Møller, Niels, Jessen, Niels
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 15.04.2015
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adult; AMP-Activated Protein Kinases - metabolism; Autophagy; Autophagy-Related Protein-1 Homolog; Blood Glucose; Cross-Over Studies; Exercise; Exercise - physiology; Fasting - physiology; Fatty Acids, Nonesterified - blood; Healthy Volunteers; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Male; Microtubule-Associated Proteins - metabolism; Muscle, Skeletal - metabolism; Musculoskeletal system; Nutritional Status; Phosphorylation; Physiology; Protein-Serine-Threonine Kinases - metabolism; Random Allocation; Sequestosome-1 Protein; Young Adult; nutritional status; ULK1; autophagy signaling; skeletal muscle; human; exercise training
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01116.2014

Data from transgenic animal models suggest that exercise-induced autophagy is critical for adaptation to physical training, and that Unc-51 like kinase-1 (ULK1) serves as an important regulator of autophagy. Phosphorylation of ULK1 at Ser(555) stimulates autophagy, whereas phosphorylation at Ser(757) is inhibitory. To determine whether exercise regulates ULK1 phosphorylation in humans in vivo in a nutrient-dependent manner, we examined skeletal muscle biopsies from healthy humans after 1-h cycling exercise at 50% maximal O2 uptake on two occasions: 1) during a 36-h fast, and 2) during continuous glucose infusion at 0.2 kg/h. Physical exercise increased ULK1 phosphorylation at Ser(555) and decreased lipidation of light chain 3B. ULK1 phosphorylation at Ser(555) correlated positively with AMP-activated protein kinase-α Thr(172) phosphorylation and negatively with light chain 3B lipidation. ULK1 phosphorylation at Ser(757) was not affected by exercise. Fasting increased ULK1 and p62 protein expression, but did not affect exercise-induced ULK1 phosphorylation. These data demonstrate that autophagy signaling is activated in human skeletal muscle after 60 min of exercise, independently of nutritional status, and suggest that initiation of autophagy constitutes an important physiological response to exercise in humans.