Cell Reports
Volume 21, Issue 6, 7 November 2017, Pages 1507-1520
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Article
The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

https://doi.org/10.1016/j.celrep.2017.10.040Get rights and content
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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

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.

Keywords

skeletal muscle
exercise
Eif6
systems biology
metabolism
mitochondria
network biology

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