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      mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

      review-article
      Frontiers in Physiology
      Frontiers Media S.A.
      mTOR, skeletal muscle, hypertrophy, atrophy, sarcopenia

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          Abstract

          Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrophy and muscle wastage. This review will highlight the fundamental role of mTOR in skeletal muscle growth by summarizing the phenotype of skeletal-specific mTOR deficiency. In addition, the evidence that mTOR is a dual regulator of anabolism and catabolism in skeletal muscle mass will be discussed. A full understanding of mTOR signaling in the maintenance of skeletal muscle mass could help to develop mTOR-targeted therapeutics to prevent muscle wasting.

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          Most cited references57

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          mTOR Signaling in Growth, Metabolism, and Disease.

          The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.
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            Growing roles for the mTOR pathway.

            The mammalian TOR (mTOR) pathway is a key regulator of cell growth and proliferation and increasing evidence suggests that its deregulation is associated with human diseases, including cancer and diabetes. The mTOR pathway integrates signals from nutrients, energy status and growth factors to regulate many processes, including autophagy, ribosome biogenesis and metabolism. Recent work identifying two structurally and functionally distinct mTOR-containing multiprotein complexes and TSC1/2, rheb, and AMPK as upstream regulators of mTOR is beginning to reveal how mTOR can sense diverse signals and produce a myriad of responses.
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              Signal integration by mTORC1 coordinates nutrient input with biosynthetic output.

              Flux through metabolic pathways is inherently sensitive to the levels of specific substrates and products, but cellular metabolism is also managed by integrated control mechanisms that sense the nutrient and energy status of a cell or organism. The mechanistic target of rapamycin complex 1 (mTORC1), a protein kinase complex ubiquitous to eukaryotic cells, has emerged as a critical signalling node that links nutrient sensing to the coordinated regulation of cellular metabolism. Here, we discuss the role of mTORC1 as a conduit between cellular growth conditions and the anabolic processes that promote cell growth. The emerging network of signalling pathways through which mTORC1 integrates systemic signals (secreted growth factors) with local signals (cellular nutrients - amino acids, glucose and oxygen - and energy, ATP) is detailed. Our expanding understanding of the regulatory network upstream of mTORC1 provides molecular insights into the integrated sensing mechanisms by which diverse cellular signals converge to control cell physiology.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                17 October 2017
                2017
                : 8
                : 788
                Affiliations
                Department of Molecular Medicine, School of Medicine, Gachon University , Incheon, South Korea
                Author notes

                Edited by: Bert Blaauw, Università degli Studi di Padova, Italy

                Reviewed by: John Joseph McCarthy, University of Kentucky, United States; Kunihiro Sakuma, Tokyo Institute of Technology, Japan

                *Correspondence: Mee-Sup Yoon msyoon@ 123456gachon.ac.kr

                This article was submitted to Striated Muscle Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2017.00788
                5650960
                29089899
                2ef4a622-e93e-4991-ae22-58ce6d790910
                Copyright © 2017 Yoon.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 July 2017
                : 26 September 2017
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 91, Pages: 9, Words: 7436
                Funding
                Funded by: Ministry of Education 10.13039/100010449
                Award ID: 2015R1D1A1A01058313
                Funded by: Gachon University Gil Medical Center 10.13039/501100006107
                Award ID: 2015-15
                Funded by: Korea Health Industry Development Institute 10.13039/501100003710
                Award ID: HI17C0426
                Categories
                Physiology
                Review

                Anatomy & Physiology
                mtor,skeletal muscle,hypertrophy,atrophy,sarcopenia
                Anatomy & Physiology
                mtor, skeletal muscle, hypertrophy, atrophy, sarcopenia

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