The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks
| Autor: | Martin Hrabé de Angelis, Claude Bouchard, Deborah M. Simpson, Peter K. Davidsen, Alessandra Scagliola, Izwan Bharudin, Robert J. Beynon, Addolorata Pisconti, Francesco Falciani, Jan Rozman, Farhat L. Khanim, Claire E. Stewart, Mark X. Caddick, Malcolm J. Jackson, Michela Bonomo, Stefano Biffo, Mark A. Sarzynski, Sujoy Ghosh, Kim Clarke, Daniela Brina, Stuart Egginton, John M. Ankers, Timothy Pearson, Christopher M. Bunce, Sara Ricciardi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteome Transcription Genetic network biology Regulator Gene regulatory network Mitochondrion RC1200 Mice 0302 clinical medicine Tandem Mass Spectrometry Gene Regulatory Networks Eif6 Exercise Metabolism Mitochondria Network Biology Skeletal Muscle Systems Biology Eukaryotic Initiation Factors lcsh:QH301-705.5 Chromatography High Pressure Liquid Oligonucleotide Array Sequence Analysis Mice Knockout Gene knockdown Acetylation systems biology Cell biology Up-Regulation medicine.anatomical_structure Systems biology Down-Regulation Biology Calorimetry General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Endurance training Physical Conditioning Animal medicine Animals Humans skeletal muscle Muscle Skeletal Skeletal muscle Mice Inbred C57BL Oxygen 030104 developmental biology lcsh:Biology (General) Energy Metabolism Reactive Oxygen Species Ribosomes metabolism 030217 neurology & neurosurgery Homeostasis |
| Zdroj: | Cell Reports, Vol 21, Iss 6, Pp 1507-1520 (2017) Cell Reports Cell Rep. 21, 1507-1520 (2017) |
| ISSN: | 2211-1247 |
| Popis: | Summary 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. Graphical Abstract Highlights • Endurance exercise profoundly affects the structure of gene networks • Eif6 is a hub in gene networks responsible for muscle metabolism and protein synthesis • Mitochondrial metabolic capacity altered in muscle from Eif6+/− mice • Eif6 haploinsufficiency increased ROS generation and reduced exercise performance Clarke et al. use data-driven reverse engineering to uncover the role of Eif6 in controlling skeletal muscle homeostasis. They achieve this by analyzing the complex network of genes that controls skeletal muscle adaptation to endurance exercise, together with in vivo studies of eif6+/− mice that show decreased respiration efficiency, increased ROS production, and reduced exercise performance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|