| RRC ID |
64289
|
| 著者 |
Hunt LC, Schadeberg B, Stover J, Haugen B, Pagala V, Wang YD, Puglise J, Barton ER, Peng J, Demontis F.
|
| タイトル |
Antagonistic control of myofiber size and muscle protein quality control by the ubiquitin ligase UBR4 during aging.
|
| ジャーナル |
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.
|
| 巻・号 |
12(1)
|
| ページ |
1418
|
| 公開日 |
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
|
| リソース情報 |
| ショウジョウバエ |
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