The regulation of exercise-mediated skeletal muscle function: the role of protein ubiquitylation

Lord, Samuel Oliver (2021). The regulation of exercise-mediated skeletal muscle function: the role of protein ubiquitylation. University of Birmingham. M.Sc.

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Abstract

Skeletal muscle is a dynamic tissue responsible for maintaining healthy functioning of the human body. Failure in maintaining skeletal muscle health can cause deleterious effects such as metabolic diseases. Ubiquitylation is a post-translational modification known to regulate most biological processes in eukaryotic cells through both degradative and non- degradative mechanisms. Evidence suggests that ubiquitylation plays a fundamental role in protein degradation, controlling protein quality control in skeletal muscle. However, ubiquitylation currently remains a poorly established process with respect to its complexity. Exercise is a well-established physiological stimulus for improving skeletal muscle health and preventing, attenuating or offsetting impaired skeletal muscle function. Therefore, understanding how ubiquitylation is mediated by exercise will help to identify novel therapeutic strategies to improve skeletal muscle health. In this thesis, I will review some existing knowledge on exercise-mediated ubiquitylation in skeletal muscle. Previous work has indicated that exercise can promote protein degradation. As a result, the majority of research investigating exercise-mediated ubiquitylation has focused on ubiquitin-mediated protein degradation. These studies have commonly utilised targeted approaches by investigating individual proteins. Recent efforts have harnessed mass spectrometry-based proteomics for studying exercise-mediated ubiquitylation in skeletal muscle, providing an unbiased and more comprehensive investigation of this post-translational modification. However, the current proteomic methods to detect protein ubiquitylation in primary tissue sample, such as skeletal muscle, lacks sensitivity and so requires further improvements. Therefore, we will finally suggest improved methods for analysing exercise-mediated ubiquitylation in whole skeletal muscle proteome alongside providing some of the ongoing research I have conducted to validate their effectiveness.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):