Reference - Detail
| RRC ID | 64289 |
|---|---|
| Author | Hunt LC, Schadeberg B, Stover J, Haugen B, Pagala V, Wang YD, Puglise J, Barton ER, Peng J, Demontis F. |
| Title | Antagonistic control of myofiber size and muscle protein quality control by the ubiquitin ligase UBR4 during aging. |
| Journal | Nat Commun |
| Abstract |
Sarcopenia is a degenerative condition that consists in age-induced atrophy and functional decline of skeletal muscle cells (myofibers). A common hypothesis is that inducing myofiber hypertrophy should also reinstate myofiber contractile function but such model has not been extensively tested. Here, we find that the levels of the ubiquitin ligase UBR4 increase in skeletal muscle with aging, and that UBR4 increases the proteolytic activity of the proteasome. Importantly, muscle-specific UBR4 loss rescues age-associated myofiber atrophy in mice. However, UBR4 loss reduces the muscle specific force and accelerates the decline in muscle protein quality that occurs with aging in mice. Similarly, hypertrophic signaling induced via muscle-specific loss of UBR4/poe and of ESCRT members (HGS/Hrs, STAM, USP8) that degrade ubiquitinated membrane proteins compromises muscle function and shortens lifespan in Drosophila by reducing protein quality control. Altogether, these findings indicate that these ubiquitin ligases antithetically regulate myofiber size and muscle protein quality control. |
| Volume | 12(1) |
| Pages | 1418 |
| Published | 2021-3-3 |
| DOI | 10.1038/s41467-021-21738-8 |
| PII | 10.1038/s41467-021-21738-8 |
| PMID | 33658508 |
| PMC | PMC7930053 |
| MeSH | Aging / physiology* Animals Animals, Genetically Modified Autophagy / physiology Calmodulin-Binding Proteins / genetics Calmodulin-Binding Proteins / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Female Lysosomes / metabolism Male Mice, Inbred C57BL Mice, Knockout Muscle Fibers, Skeletal / metabolism Muscle Fibers, Skeletal / physiology* Muscle Proteins / metabolism* Muscle, Skeletal / pathology Muscle, Skeletal / physiology Proteolysis Ubiquitin / metabolism Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 21 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| Drosophila | |