ArticleProceedings of the National Academy of Sciences of the United States of America2011
Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Chemotherapy-induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol.Journal of cachexia, sarcopenia and muscle · 2019Trial
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Metabolic dysregulation contributes to the development of dysferlinopathy.Life science alliance · 2025Article
- Muscle mTOR controls iron homeostasis and ferritinophagy via NRF2, HIFs and AKT/PKB signaling pathways.Cellular and molecular life sciences : CMLS · 2025Article
- mTORC1 in energy expenditure: consequences for obesity.Nature reviews. Endocrinology · 2024Review
- Adult skeletal muscle peroxisome proliferator-activated receptor γ -related coactivator 1 is involved in maintaining mitochondrial content.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Thyroid hormone regulates glutamine metabolism and anaplerotic fluxes by inducing mitochondrial glutamate aminotransferase GPT2.Cell reports · 2022Article
- AKT controls protein synthesis and oxidative metabolism via combined mTORC1 and FOXO1 signalling to govern muscle physiology.Journal of cachexia, sarcopenia and muscle · 2022Article
- Berberine attenuates fructose-induced insulin resistance by stimulating the hepatic LKB1/AMPK/PGC1α pathway in mice.Pharmaceutical biology · 2020Article
- mTORC1 signalling is not essential for the maintenance of muscle mass and function in adult sedentary mice.Journal of cachexia, sarcopenia and muscle · 2020Article
- Restoration of skeletal muscle homeostasis by hydrogen sulfide during hyperhomocysteinemia-mediated oxidative/ER stress conditionCanadian journal of physiology and pharmacology · 2019Review
- Review
- Lack of muscle mTOR kinase activity causes early onset myopathy and compromises whole-body homeostasis.Journal of cachexia, sarcopenia and muscle · 2019Article
- Phosphorylation of Acetyl-CoA Carboxylase by AMPK Reduces Renal Fibrosis and Is Essential for the Anti-Fibrotic Effect of Metformin.Journal of the American Society of Nephrology : JASN · 2018Article
- A Skeletal Muscle Model of Infantile-onset Pompe Disease with Patient-specific iPS Cells.Scientific reports · 2017Article
- mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold.Scientific reports · 2016Article
- Mitochondria are required for pro-ageing features of the senescent phenotype.The EMBO journal · 2016Article
- Alterations to mTORC1 signaling in the skeletal muscle differentially affect whole-body metabolism.Skeletal muscle · 2016Article
- Loss of mTOR signaling affects cone function, cone structure and expression of cone specific proteins without affecting cone survival.Experimental eye research · 2015Article
- Agonism of the 5-hydroxytryptamine 1F receptor promotes mitochondrial biogenesis and recovery from acute kidney injury.The Journal of pharmacology and experimental therapeutics · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-α (PGC-1α), 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-1α 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-1α 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-1α. However, our data also show that the impairment of mitochondria does not lead directly to the lethal myopathy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.