PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase

• Published in: Nature communications Vol. 11; no. 1; pp. 174 - 15
• Main Authors: D’Hulst, Gommaar, Soro-Arnaiz, Inés, Masschelein, Evi, Veys, Koen, Fitzgerald, Gillian, Smeuninx, Benoit, Kim, Sunghoon, Deldicque, Louise, Blaauw, Bert, Carmeliet, Peter, Breen, Leigh, Koivunen, Peppi, Zhao, Shi-Min, De Bock, Katrien
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 13/51; 13/95; 14/19; 38/35; 38/77; 631/80/304; 631/80/83/2359; 64/60; 692/308/2778; 82/29; 82/58; 96/95; Activation; Adult; Aged; Aging - metabolism; Amino acids; Amino Acids - metabolism; Animals; Degradation; Depletion; Disease Models, Animal; Female; Geriatrics; Growth factors; HEK293 Cells; Humanities and Social Sciences; Humans; Hydroxylation; Hypoxia-Inducible Factor-Proline Dioxygenases - metabolism; Leucine; Leucine - metabolism; Leucine-tRNA Ligase - metabolism; Male; Mechanistic Target of Rapamycin Complex 1 - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Muscle Development; Muscles; Muscles - metabolism; Muscles - pathology; Nutrient content; Nutrients; Oxygen; Oxygen - metabolism; Oxygen probes; Procollagen-Proline Dioxygenase - genetics; Procollagen-Proline Dioxygenase - metabolism; Prolyl hydroxylase; Science; Science (multidisciplinary); Sensors; Signal Transduction; tRNA Leu

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 (PHD1 KO ) reduces muscle mass. PHD1 KO muscles show impaired mTORC1 activation in response...