PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase
| العنوان: | PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase |
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| المؤلفون: | Peter Carmeliet, Louise Deldicque, Sunghoon Kim, Shimin Zhao, Leigh Breen, Gillian Fitzgerald, Koen Veys, Peppi Koivunen, Benoit Smeuninx, Inés Soro-Arnaiz, Katrien De Bock, Bert Blaauw, Gommaar D'Hulst, Evi Masschelein |
| المساهمون: | UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature communications, vol 11, iss 1 Nature Communications, 11 Nature Communications Nature Communications, Vol. 11, no. 1, p. 174 (2020) |
| بيانات النشر: | Nature Portfolio, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Aging, Regulator, General Physics and Astronomy, mTORC1, Inbred C57BL, Muscle Development, Hydroxylation, chemistry.chemical_compound, Mice, 0302 clinical medicine, Amino Acids, lcsh:Science, Mice, Knockout, chemistry.chemical_classification, Multidisciplinary, Muscles, Amino acid, Cell biology, Mechanisms of disease, TOR signalling, Female, Leucine, Signal transduction, biological phenomena, cell phenomena, and immunity, Signal Transduction, Gene isoform, Adult, Knockout, Science, Procollagen-Proline Dioxygenase, Genetics and Molecular Biology, Mechanistic Target of Rapamycin Complex 1, Article, General Biochemistry, Genetics and Molecular Biology, Hypoxia-Inducible Factor-Proline Dioxygenases, 03 medical and health sciences, Clinical Research, Animals, Humans, Aged, Animal, Leucyl-tRNA synthetase, General Chemistry, Mice, Inbred C57BL, Oxygen, Disease Models, Animal, 030104 developmental biology, HEK293 Cells, chemistry, Preclinical research, General Biochemistry, Disease Models, lcsh:Q, Leucine-tRNA Ligase, 030217 neurology & neurosurgery |
| الوصف: | mTORC1 is an important regulator of muscle mass but how it is modulated by oxygen and nutrients is not completely understood. We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mice (PHD1KO) reduces muscle mass. PHD1KO muscles show impaired mTORC1 activation in response to leucine whereas mTORC1 activation by growth factors or eccentric contractions was preserved. The ability of PHD1 to promote mTORC1 activity is independent of its hydroxylation activity but is caused by decreased protein content of the leucyl tRNA synthetase (LRS) leucine sensor. Mechanistically, PHD1 interacts with and stabilizes LRS. This interaction is promoted during oxygen and amino acid depletion and protects LRS from degradation. Finally, elderly subjects have lower PHD1 levels and LRS activity in muscle from aged versus young human subjects. In conclusion, PHD1 ensures an optimal mTORC1 response to leucine after episodes of metabolic scarcity. Nature Communications, 11 ISSN:2041-1723 |
| وصف الملف: | Electronic; application/pdf; application/application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed65d3a9ba21caa35226b725b5c4e464Test https://doaj.org/article/57ce964136154da49cd0e8f1b72242c1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ed65d3a9ba21caa35226b725b5c4e464 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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