Journal article
The Unfolded Protein Response Mediates Adaptation to Exercise in Skeletal Muscle through a PGC-1α/ATF6α Complex
Cell metabolism, Vol.13(2), pp.160-169
2011
DOI: 10.1016/j.cmet.2011.01.003
PMCID: PMC3057411
PMID: 21284983
Abstract
Exercise has been shown to be effective for treating obesity and type 2 diabetes. However, the molecular mechanisms for adaptation to exercise training are not fully understood. Endoplasmic reticulum (ER) stress has been linked to metabolic dysfunction. Here we show that the unfolded protein response (UPR), an adaptive response pathway that maintains ER homeostasis upon luminal stress, is activated in skeletal muscle during exercise and adapts skeletal muscle to exercise training. The transcriptional coactivator PGC-1α, which regulates several exercise-associated aspects of skeletal muscle function, mediates the UPR in myotubes and skeletal muscle through coactivation of ATF6α. Efficient recovery from acute exercise is compromised in
ATF6α
−/− mice. Blocking ER-stress-related cell death via deletion of CHOP partially rescues the exercise intolerance phenotype in muscle-specific PGC-1α KO mice. These findings suggest that modulation of the UPR through PGC1α represents an alternative avenue to improve skeletal muscle function and achieve metabolic benefits.
► The UPR is activated in skeletal muscle during exercise ► PGC-1
α regulates the UPR in myotubes and skeletal muscle via coactivation of ATF6
α ► Exercise training leads to adaptation in skeletal muscle through ATF6
α-mediated UPR ► CHOP null mutation partially rescues exercise intolerance of MKO-PGC-1
α mice
Details
- Title: Subtitle
- The Unfolded Protein Response Mediates Adaptation to Exercise in Skeletal Muscle through a PGC-1α/ATF6α Complex
- Creators
- Jun Wu - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAJorge L Ruas - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAJennifer L Estall - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAKyle A Rasbach - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAJang Hyun Choi - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USALi Ye - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAPontus Boström - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAHeather M Tyra - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USARobert W Crawford - Howard Hughes Medical Institute, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAKevin P Campbell - Howard Hughes Medical Institute, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAD. Thomas Rutkowski - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USARandal J Kaufman - Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USABruce M Spiegelman - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.13(2), pp.160-169
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2011.01.003
- PMID
- 21284983
- PMCID
- PMC3057411
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Language
- English
- Date published
- 2011
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984020634202771
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