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

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

doi:10.1016/j.celrep.2017.10.040

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

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

Biosciences

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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.

Original language	English
Pages (from-to)	1507-1520
Number of pages	14
Journal	Cell Reports
Volume	21
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2017.10.040
Publication status	Published - 7 Nov 2017

Keywords

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

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Clarke_et_al_The_role_of_Eif6_skeletal_muscle_Cell_Reports_2017
Published in Cell Reports on 07/11/2017 DOI: 10.1016/j.celrep.2017.10.040
Final published version, 4.31 MBLicence: Creative Commons: Attribution (CC BY)

https://www.sciencedirect.com/science/article/pii/S2211124717314870Licence: Creative Commons: Attribution (CC BY)

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Clarke, K., Ricciardi, S., Pearson, T., Bharudin, I., Davidsen, P. K., Bonomo, M., Brina, D., Scagliola, A., Simpson, D. M., Beynon, R. J., Khanim, F., Ankers, J., Sarzynski, M. A., Ghosh, S., Pisconti, A., Rozman, J., Hrabe de Angelis, M., Bunce, C., Stewart, C., ... Falciani, F. (2017). The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks. Cell Reports, 21(6), 1507-1520. https://doi.org/10.1016/j.celrep.2017.10.040

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

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.",

keywords = "Journal Article, skeletal muscle exercise Eif6 , systems biology , metabolism , mitochondria , network biology",

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

year = "2017",

month = nov,

day = "7",

doi = "10.1016/j.celrep.2017.10.040",

language = "English",

volume = "21",

pages = "1507--1520",

journal = "Cell Reports",

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Clarke, K, Ricciardi, S, Pearson, T, Bharudin, I, Davidsen, PK, Bonomo, M, Brina, D, Scagliola, A, Simpson, DM, Beynon, RJ, Khanim, F, Ankers, J, Sarzynski, MA, Ghosh, S, Pisconti, A, Rozman, J, Hrabe de Angelis, M, Bunce, C, Stewart, C, Egginton, S, Caddick, M, Jackson, M, Bouchard, C, Biffo, S & Falciani, F 2017, 'The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks', Cell Reports, vol. 21, no. 6, pp. 1507-1520. https://doi.org/10.1016/j.celrep.2017.10.040

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T1 - The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

AU - Clarke, Kim

AU - Ricciardi, Sara

AU - Pearson, Tim

AU - Bharudin, Izwan

AU - Davidsen, Peter K.

AU - Bonomo, Michela

AU - Brina, Daniela

AU - Scagliola, Alessandra

AU - Simpson, Deborah M.

AU - Beynon, Robert J.

AU - Khanim, Farhat

AU - Ankers, John

AU - Sarzynski, Mark A.

AU - Ghosh, Sujoy

AU - Pisconti, Addolorata

AU - Rozman, Jan

AU - Hrabe de Angelis, Martin

AU - Bunce, Chris

AU - Stewart, Claire

AU - Egginton, Stuart

AU - Caddick, Mark

AU - Jackson, Malcolm

AU - Bouchard, Claude

AU - Biffo, Stefano

AU - Falciani, Francesco

PY - 2017/11/7

Y1 - 2017/11/7

N2 - 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.

AB - 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.

KW - Journal Article

KW - skeletal muscle exercise Eif6

KW - systems biology

KW - metabolism

KW - mitochondria

KW - network biology

U2 - 10.1016/j.celrep.2017.10.040

DO - 10.1016/j.celrep.2017.10.040

M3 - Article

C2 - 29117557

SN - 2211-1247

VL - 21

SP - 1507

EP - 1520

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

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

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Keywords

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