{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:23:53Z","timestamp":1791113033596,"version":"4.1.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,12,20]]},"abstract":"<jats:p>Mammalian target of rapamycin complex 1 (mTORC1) is central to the control of cell, organ, and body size. Skeletal muscle-specific inactivation of mTORC1 in mice results in smaller muscle fibers, fewer mitochondria, increased glycogen stores, and a progressive myopathy that causes premature death. In mTORC1-deficient muscles, peroxisome proliferator-activated receptor gamma coactivator 1-\u03b1 (PGC-1\u03b1), which regulates mitochondrial biogenesis and glucose homeostasis, is strongly down-regulated. Here we tested whether induction of mitochondrial biogenesis pharmacologically or by the overexpression of PGC-1\u03b1 is sufficient to reverse the phenotype of mice deficient for mTORC1. We show that both approaches normalize mitochondrial function, such as oxidative capacity and expression of mitochondrial genes. However, they do not prevent or delay the progressive myopathy. In addition, we find that mTORC1 has a much stronger effect than PGC-1\u03b1 on the glycogen content in muscle. This effect is based on the strong activation of PKB\/Akt in mTORC1-deficient mice. We also show that activation of PKB\/Akt not only affects glycogen synthesis but also diminishes glycogen degradation. Thus, our work provides strong functional evidence that mitochondrial dysfunction in mice with inactivated mTORC1 signaling is caused by the down-regulation of PGC-1\u03b1. However, our data also show that the impairment of mitochondria does not lead directly to the lethal myopathy.<\/jats:p>","DOI":"10.1073\/pnas.1111448109","type":"journal-article","created":{"date-parts":[[2011,12,6]],"date-time":"2011-12-06T01:52:38Z","timestamp":1323136358000},"page":"20808-20813","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function"],"prefix":"10.1073","volume":"108","author":[{"given":"Klaas","family":"Romanino","sequence":"first","affiliation":[{"name":"Biozentrum, University of Basel, 4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Mazelin","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5239, \u00c9cole Normale Sup\u00e9rieure de Lyon, Laboratoire de Biologie Mol\u00e9culaire de la Cellule, Equipe Diff\u00e9renciation Neuromusculaire, Universit\u00e9 Lyon 1; Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Albert","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, 4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Conjard-Duplany","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et Physiopathologie M\u00e9taboliques, Equipe d'Accueil Universitaire, Facult\u00e9 de M\u00e9decine Lyon Est, Universit\u00e9 de Lyon, La Buire, 69372 Lyon Cedex 8, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Lin","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, 4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Florian","family":"Bentzinger","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, 4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Handschin","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, 4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pere","family":"Puigserver","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute and"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Zorzato","sequence":"additional","affiliation":[{"name":"Departments of fAnesthesia and"},{"name":"Biomedicine, Basel University Hospital, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5239, \u00c9cole Normale Sup\u00e9rieure de Lyon, Laboratoire de Biologie Mol\u00e9culaire de la Cellule, Equipe Diff\u00e9renciation Neuromusculaire, Universit\u00e9 Lyon 1; Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann-Ga\u00ebl","family":"Gangloff","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5239, \u00c9cole Normale Sup\u00e9rieure de Lyon, Laboratoire de Biologie Mol\u00e9culaire de la Cellule, Equipe Diff\u00e9renciation Neuromusculaire, Universit\u00e9 Lyon 1; Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"R\u00fcegg","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, 4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,12,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2005.04.018"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.016"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903131"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.10.002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02866"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80611-X"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707006200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06322"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704817200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1525107"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1701"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-4-14"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.07.006"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607795103"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911570106"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00904"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604893104"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00167.2002"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05861"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-0068-4"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2247"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.10.008"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1111448109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:39:24Z","timestamp":1649795964000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1111448109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,5]]},"references-count":23,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2011,12,20]]}},"alternative-id":["10.1073\/pnas.1111448109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1111448109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,5]]},"assertion":[{"value":"2011-12-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}