Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control
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 syst...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/2/407 |
| _version_ | 1797411578170048512 |
|---|---|
| author | Dulce Peris-Moreno Laura Cussonneau Lydie Combaret Cécile Polge Daniel Taillandier |
| author_facet | Dulce Peris-Moreno Laura Cussonneau Lydie Combaret Cécile Polge Daniel Taillandier |
| author_sort | Dulce Peris-Moreno |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T04:48:10Z |
| format | Article |
| id | doaj.art-a59443eb401f45da9c964e97303b3f06 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:48:10Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a59443eb401f45da9c964e97303b3f062023-12-03T13:14:02ZengMDPI AGMolecules1420-30492021-01-0126240710.3390/molecules26020407Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy ControlDulce Peris-Moreno0Laura Cussonneau1Lydie Combaret2Cécile Polge3Daniel Taillandier4Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne, F-63000 Clermont-Ferrand, FranceUnité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne, F-63000 Clermont-Ferrand, FranceUnité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne, F-63000 Clermont-Ferrand, FranceUnité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne, F-63000 Clermont-Ferrand, FranceUnité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne, F-63000 Clermont-Ferrand, FranceSkeletal 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.https://www.mdpi.com/1420-3049/26/2/407skeletal muscle atrophyhypertrophyE3 ubiquitin ligaseMuRF1MAFbxanabolism |
| spellingShingle | Dulce Peris-Moreno Laura Cussonneau Lydie Combaret Cécile Polge Daniel Taillandier Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control Molecules skeletal muscle atrophy hypertrophy E3 ubiquitin ligase MuRF1 MAFbx anabolism |
| title | Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control |
| title_full | Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control |
| title_fullStr | Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control |
| title_full_unstemmed | Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control |
| title_short | Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control |
| title_sort | ubiquitin ligases at the heart of skeletal muscle atrophy control |
| topic | skeletal muscle atrophy hypertrophy E3 ubiquitin ligase MuRF1 MAFbx anabolism |
| url | https://www.mdpi.com/1420-3049/26/2/407 |
| work_keys_str_mv | AT dulceperismoreno ubiquitinligasesattheheartofskeletalmuscleatrophycontrol AT lauracussonneau ubiquitinligasesattheheartofskeletalmuscleatrophycontrol AT lydiecombaret ubiquitinligasesattheheartofskeletalmuscleatrophycontrol AT cecilepolge ubiquitinligasesattheheartofskeletalmuscleatrophycontrol AT danieltaillandier ubiquitinligasesattheheartofskeletalmuscleatrophycontrol |