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

Research output: Contribution to journalArticle

Authors

  • Kim Clarke
  • Sara Ricciardi
  • Tim Pearson
  • Izwan Bharudin
  • Peter K. Davidsen
  • Michela Bonomo
  • Daniela Brina
  • Alessandra Scagliola
  • Deborah M. Simpson
  • Robert J. Beynon
  • John Ankers
  • Mark A. Sarzynski
  • Sujoy Ghosh
  • Addolorata Pisconti
  • Jan Rozman
  • Martin Hrabe de Angelis
  • Claire Stewart
  • Stuart Egginton
  • Mark Caddick
  • Malcolm Jackson
  • Claude Bouchard
  • Stefano Biffo
  • Francesco Falciani

Colleges, School and Institutes

External organisations

  • University of Liverpool
  • Molecular Histology and Cell Growth Unit, INGM - Fondazione Istituto Nazionale Genetica Molecolare
  • University of East Anglia
  • School of Biosciences and Biotechnology, Universiti Kebangsaan Malaysia
  • Pennington Biomedical Research Center
  • German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
  • Liverpool John Moores University
  • University of Leeds
  • Dipartimento di Bioscienze, Università degli Studi di Milano

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.

Details

Original languageEnglish
Pages (from-to)1507-1520
Number of pages14
JournalCell Reports
Volume21
Issue number6
Publication statusPublished - 7 Nov 2017

Keywords

  • Journal Article, skeletal muscle exercise Eif6 , systems biology , metabolism , mitochondria , network biology