Tags

Type your tag names separated by a space and hit enter

PGC-1α promotes exercise-induced autophagy in mouse skeletal muscle.
Physiol Rep 2016; 4(3)PR

Abstract

Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise-induced autophagy remain unclear, although the muscle oxidative phenotype has been linked with basal autophagy levels. Therefore, the aim of this study was to investigate the role of the key regulator of muscle oxidative capacity, PGC-1α, in exercise-induced autophagy at several time points during recovery. Mice with transgenic muscle-specific overexpression (TG) or knockout (MKO) of PGC-1α and their respective littermate controls were subjected to a single 1 h bout of treadmill running and euthanized immediately (0 h), 2, 6, and 10 h after exercise. In the PGC-1α MKO strain, quadriceps protein content of the autophagy marker LC3II was increased from 2 h into recovery in lox/lox control, but not in MKO mice. In the PGC-1α TG strain, quadriceps protein content of LC3II was increased from 2 h after exercise in TG, but not in WT. Although AMPK and ACC phosphorylation was increased immediately following exercise, the observed exercise-induced autophagy response was not associated with phosphorylation of the AMPK-target ULK1. However, lower protein carbonyl content was observed in lox/lox and TG mice after exercise coinciding with the increased LC3 lipidation. In conclusion, the present results suggest a role of skeletal muscle PGC-1α in coordinating several exercise-induced adaptive responses including autophagic removal of damaged cellular components.

Authors+Show Affiliations

Department of Biology, Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark.Department of Biology, Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark.Department of Biology, Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark.Department of Biology, Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark.Department of Biology, Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark hpilegaard@bio.ku.dk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26869683

Citation

Halling, Jens F., et al. "PGC-1α Promotes Exercise-induced Autophagy in Mouse Skeletal Muscle." Physiological Reports, vol. 4, no. 3, 2016.
Halling JF, Ringholm S, Nielsen MM, et al. PGC-1α promotes exercise-induced autophagy in mouse skeletal muscle. Physiol Rep. 2016;4(3).
Halling, J. F., Ringholm, S., Nielsen, M. M., Overby, P., & Pilegaard, H. (2016). PGC-1α promotes exercise-induced autophagy in mouse skeletal muscle. Physiological Reports, 4(3), doi:10.14814/phy2.12698.
Halling JF, et al. PGC-1α Promotes Exercise-induced Autophagy in Mouse Skeletal Muscle. Physiol Rep. 2016;4(3) PubMed PMID: 26869683.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PGC-1α promotes exercise-induced autophagy in mouse skeletal muscle. AU - Halling,Jens F, AU - Ringholm,Stine, AU - Nielsen,Maja M, AU - Overby,Peter, AU - Pilegaard,Henriette, PY - 2016/2/13/entrez PY - 2016/2/13/pubmed PY - 2016/2/13/medline KW - Autophagy KW - PGC‐1α KW - exercise JF - Physiological reports JO - Physiol Rep VL - 4 IS - 3 N2 - Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise-induced autophagy remain unclear, although the muscle oxidative phenotype has been linked with basal autophagy levels. Therefore, the aim of this study was to investigate the role of the key regulator of muscle oxidative capacity, PGC-1α, in exercise-induced autophagy at several time points during recovery. Mice with transgenic muscle-specific overexpression (TG) or knockout (MKO) of PGC-1α and their respective littermate controls were subjected to a single 1 h bout of treadmill running and euthanized immediately (0 h), 2, 6, and 10 h after exercise. In the PGC-1α MKO strain, quadriceps protein content of the autophagy marker LC3II was increased from 2 h into recovery in lox/lox control, but not in MKO mice. In the PGC-1α TG strain, quadriceps protein content of LC3II was increased from 2 h after exercise in TG, but not in WT. Although AMPK and ACC phosphorylation was increased immediately following exercise, the observed exercise-induced autophagy response was not associated with phosphorylation of the AMPK-target ULK1. However, lower protein carbonyl content was observed in lox/lox and TG mice after exercise coinciding with the increased LC3 lipidation. In conclusion, the present results suggest a role of skeletal muscle PGC-1α in coordinating several exercise-induced adaptive responses including autophagic removal of damaged cellular components. SN - 2051-817X UR - https://www.unboundmedicine.com/medline/citation/26869683/PGC_1α_promotes_exercise_induced_autophagy_in_mouse_skeletal_muscle_ L2 - https://doi.org/10.14814/phy2.12698 DB - PRIME DP - Unbound Medicine ER -