Journal
MOLECULES
Volume 26, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/molecules26020407
Keywords
skeletal muscle atrophy; hypertrophy; E3 ubiquitin ligase; MuRF1; MAFbx; anabolism; catabolism; signaling; therapy; treatment
Funding
- AFM/Telethon [19521]
- French government IDEX-ISITE initiative [16-IDEX-0001, CAP 20e25]
- Fondation pour la Recherche Medicale [DEQ20180339180]
- CNES (Centre national d'etudes spatiales) [DAR 4800001057]
- European Union [813599]
- Marie Curie Actions (MSCA) [813599] Funding Source: Marie Curie Actions (MSCA)
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Skeletal muscle loss is a harmful side effect of chronic diseases, increasing mortality and morbidity. The ubiquitin proteasome system plays a key role in regulating muscle contraction and metabolism through targeting key proteins for degradation or activity modulation via E3 ubiquitin ligases.
Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be down-regulated. The ubiquitin proteasome system (UPS) is a master regulator of skeletal muscle that impacts muscle contractile properties and metabolism through multiple levers like signaling pathways, contractile apparatus degradation, etc. Among the different actors of the UPS, the E3 ubiquitin ligases specifically target key proteins for either degradation or activity modulation, thus controlling both pro-anabolic or pro-catabolic factors. The atrogenes MuRF1/TRIM63 and MAFbx/Atrogin-1 encode for key E3 ligases that target contractile proteins and key actors of protein synthesis respectively. However, several other E3 ligases are involved upstream in the atrophy program, from signal transduction control to modulation of energy balance. Controlling E3 ligases activity is thus a tempting approach for preserving muscle mass. While indirect modulation of E3 ligases may prove beneficial in some situations of muscle atrophy, some drugs directly inhibiting their activity have started to appear. This review summarizes the main signaling pathways involved in muscle atrophy and the E3 ligases implicated, but also the molecules potentially usable for future therapies.
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