Fractionated proteomics identifies a protein network mitigating resistance exercise-induced damage in human skeletal muscle
This study reveals molecular responses of untrained, adapted and deadapted human skeletal muscle to resistance exercise, which identifies a network of mechanosensory proteins and molecular chaperones that ensures skeleta
Resistance exercise (RE) is widely recognized for its capacity to enhance strength and increase muscle mass, offering significant benefits for human health. However, intense RE also induces acute myofibrillar damage within the skeletal muscle tissue. The molecular mechanisms responsible for preserving, marking, degrading, and restoring damaged proteins to maintain skeletal muscle function during RE remain incompletely understood.
Based on repeated sampling of human skeletal muscle, the authors demonstrate that acute, repeated, and interrupted RE induce dynamic changes in the protein landscape associated with the sarcomeric cytoskeleton. These alterations correlate with changes in phosphorylation, indicative of adaptation and deadaptation signaling footprints. The regulation primarily affects the protein network linked to the muscle maintenance protein BAG3, which includes mechanosensory proteins, small heat shock proteins, and a lipid droplet-associated protein.
All components within this network exhibit altered phosphorylation and increased cytoskeletal association following damaging RE. Furthermore, these network components cooperate to recognize strained skeletal muscle structures and mediate their degradation through chaperone-assisted selective autophagy (CASA). This process is critical for the removal of damaged proteins and the restoration of cellular integrity.
The authors' study thus identifies key regulators of skeletal muscle homeostasis in humans. These findings provide a molecular basis for understanding how skeletal muscle adapts to mechanical stress and recovers from damage. The identified network may serve as a target for future research into optimizing exercise protocols and managing muscle injury.
This research note is provided for laboratory use only. Peptides and related compounds described herein are not intended for human consumption or therapeutic use without appropriate regulatory approval. All applications must comply with local laws and institutional guidelines.