Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals.

Autor:	Segalés J; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain.; Centro Nacional de Investigaciones Cardiovasculares, 28019, Madrid, Spain., Perdiguero E; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain., Serrano AL; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain., Sousa-Victor P; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain.; Instituto de Medicina Molecular (iMM), Faculdade de Medicina, Universidade de Lisboa, 1649, Lisbon, Portugal., Ortet L; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain., Jardí M; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain., Budanov AV; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, D02 R590, Ireland.; Engelhardt Institute of Molecular Biology, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, 119991, Moscow, Russia., Garcia-Prat L; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain.; Centro Nacional de Investigaciones Cardiovasculares, 28019, Madrid, Spain.; Princess Margaret Cancer Centre, University Health Network, Toronto, M5G 1L7, ON, Canada., Sandri M; Department of Biomedical Science, University of Padova, 35100, Padova, Italy., Thomson DM; Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA., Karin M; Department of Pharmacology, University of California San Diego, La Jolla, CA, 92093, USA., Hee Lee J; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109-2200, USA., Muñoz-Cánoves P; Department of Experimental & Health Sciences, University Pompeu Fabra, CIBERNED, 08003, Barcelona, Spain. pura.munoz@upf.edu.; Centro Nacional de Investigaciones Cardiovasculares, 28019, Madrid, Spain. pura.munoz@upf.edu.; ICREA, 08003, Barcelona, Spain. pura.munoz@upf.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Jan 13; Vol. 11 (1), pp. 189. Date of Electronic Publication: 2020 Jan 13.
DOI:	10.1038/s41467-019-13832-9
Abstrakt:	A unique property of skeletal muscle is its ability to adapt its mass to changes in activity. Inactivity, as in disuse or aging, causes atrophy, the loss of muscle mass and strength, leading to physical incapacity and poor quality of life. Here, through a combination of transcriptomics and transgenesis, we identify sestrins, a family of stress-inducible metabolic regulators, as protective factors against muscle wasting. Sestrin expression decreases during inactivity and its genetic deficiency exacerbates muscle wasting; conversely, sestrin overexpression suffices to prevent atrophy. This protection occurs through mTORC1 inhibition, which upregulates autophagy, and AKT activation, which in turn inhibits FoxO-regulated ubiquitin-proteasome-mediated proteolysis. This study reveals sestrin as a central integrator of anabolic and degradative pathways preventing muscle wasting. Since sestrin also protected muscles against aging-induced atrophy, our findings have implications for sarcopenia.
Databáze:	MEDLINE
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