Author ORCID Identifier

Document Type


Date of Award


Degree Name

Master of Science (MS)


Basic Biomedical Science

First Advisor

Yifan Li


Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally discovered in neurons. UCHL1 is also expressed in skeletal muscle, but its functions remain to be fully understood. Myogenesis is a critical process involved in embryonic development, growth, and regeneration following injury. Skeletal muscle injury is prevalent in trauma and surgical procedures, and skeletal muscle ischemia-reperfusion (IR) injury is a common yet dangerous public health problem. Here we reported that UCHL1 negatively affects muscle growth during aging as well as the regeneration process following IR injury. First, we observed that UCHL1 knockdown in C2C12 myoblasts resulted in increased myotube width and differentiation. Furthermore, UCHL1 KD consistently upregulated myogenin and MyoD protein levels, key proteins involved in myogenesis, at multiple time points throughout myotube differentiation. Consistent with this in vitro result, skeletal muscle specific knockout (smKO) of UCHL1 increased muscle fiber diameter in both 1- and 2-month-old mice. Interestingly, smKO of UCHL1 caused muscle-dependent fiber type switching and myosin heavy chain expression. Following skeletal muscle IR injury, myogenin and MyoD protein expression was upregulated in injured muscle from smKO mice. In addition to this, KO mice also had increased muscle function and performance after injury compared to control mice when subjected to in situ contractile testing. UCHL1 smKO also exhibit a decreased inflammatory response following injury, as well as upregulation of proteins associated with mitophagy. As a novel finding, we also found that UCHL1 regulates p62 expression and release via deubiquitinating function. This data suggests that skeletal muscle UCHL1 may function as a negative regulator of myogenesis, both during growth, and repair following injury.

Subject Categories

Molecular Biology | Physiology


Muscle, Myogenesis, UCHL1

Number of Pages



University of South Dakota



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