Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Our work demonstrates the validity of a data-driven approach to understanding muscle homeostasis.

The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks / K. Clarke, S. Ricciardi, T. Pearson, I. Bharudin, P.K. Davidsen, M. Bonomo, D. Brina, A. Scagliola, D.M. Simpson, R.J. Beynon, F. Khanim, J. Ankers, M.A. Sarzynski, S. Ghosh, A. Pisconti, J. Rozman, M. Hrabe de Angelis, C. Bunce, C. Stewart, S. Egginton, M. Caddick, M. Jackson, C. Bouchard, S. Biffo, F. Falciani. - In: CELL REPORTS. - ISSN 2211-1247. - 21:6(2017 Nov 07), pp. 1507-1520.

The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

S. Ricciardi;A. Scagliola;S. Biffo;
2017-11-07

Abstract

Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Our work demonstrates the validity of a data-driven approach to understanding muscle homeostasis.
Eif6; exercise; metabolism; mitochondria; network biology; skeletal muscle; systems biology
Settore BIO/06 - Anatomia Comparata e Citologia
Noncoding and Translational Modulation of Gene Expression and Epigenetic Changes
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/563523
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