Expression of SUMO enzymes is fiber type dependent in skeletal muscles and is dysregulated in muscle disuse.

SUMOylation is a dynamic, reversible, enzymatic drug-targetable post-translational modification (PTM) reaction where the Small Ubiquitin-like Modifier (SUMO) moieties are attached to proteins. This reaction regulates various biological functions like cell growth, differentiation, and it is crucial for maintaining organ homeostasis. However, the actions of SUMO in skeletal muscle pathophysiology are still not investigated.

Sarcolemmal loss of active nNOS (Nos1) is an oxidative stress-dependent, early event driving disuse atrophy.

Skeletal muscle atrophy following unloading or immobilization represents a major invalidating event in bedridden patients. Among mechanisms involved in atrophy development, a controversial role is played by neuronal NOS (nNOS; NOS1), whose dysregulation at the protein level and/or subcellular distribution also characterizes other neuromuscular disorders. This study aimed to investigate unloading-induced changes in nNOS before any evidence of myofiber atrophy, using vastus lateralis biopsies obtained from young healthy subjects after a short bed-rest and rat soleus muscles after exposure to short unloading periods.

Muscle RING-finger protein-1 (MuRF1) functions and cellular localization are regulated by SUMO1 post-translational modification.

The muscle RING-finger protein-1 (MuRF1) is an E3 ubiquitin ligase expressed in skeletal and cardiac muscle tissues and it plays important roles in muscle remodeling. Upregulation of MuRF1 gene transcription participates in skeletal muscle atrophy, on contrary downregulation of protein expression leads to cardiac hypertrophy. MuRF1 gene point mutations have been found to generate protein aggregate myopathies defined as muscle disorder characterized by protein accumulation in muscle fibers.