Shared and distinct mechanisms of skeletal muscle atrophy: A narrative review

Abstract

Maintenance of skeletal muscle mass and function is an incredibly nuanced balance of anabolism and catabolism that can become distorted within different pathological conditions. In this paper we intend to discuss the distinct intracellular signaling events that regulate muscle protein atrophy for a given clinical occurrence. Aside from the common outcome of muscle deterioration, several conditions have at least one or more distinct mechanisms that creates unique intracellular environments that facilitate muscle loss. The subtle individuality to each of these given pathologies can provide both researchers and clinicians with specific targets of interest to further identify and increase the efficacy of medical treatments and interventions.

Keywords: Atrophy; Cachexia; Catabolism; Muscle loss; Muscle protein degradation; Sarcopenia.

Figure 1:

Above indicates the three major proteolytic systems that regulate skeletal muscle atrophy. Calpain activation can induce protein degradation by calcium dependent binding. The ubiquitin proteasomal system can degrade proteins through post-translational polyubiquitination through a series of E1, E2, and E3 relaying mechanisms. The polyubiquinated protein is then subsequently shuttled into the 26S proteasome for degradation. The three autophagy pathways degrade polypeptides, proteins, and organelles by integrating substrates into the lysosome. Macro-autophagy and micro-autophagy are non-specific in their degradation targets, but chaperone-mediated autophagy uses the specific pentapeptide sequence (KFERQ) to selectively bind, shuttle, and translocate proteins into the lysosome with the help of cytosolic and lysosomal heat shock cognate 71 kDa protein (Hsc70).