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Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle.
Am J Physiol Cell Physiol 2015; 308(9):C710-9AJ

Abstract

Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α.

Authors+Show Affiliations

Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada dhood@yorku.ca.

Pub Type(s)

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

Language

eng

PubMed ID

25673772

Citation

Vainshtein, Anna, et al. "Role of PGC-1α During Acute Exercise-induced Autophagy and Mitophagy in Skeletal Muscle." American Journal of Physiology. Cell Physiology, vol. 308, no. 9, 2015, pp. C710-9.
Vainshtein A, Tryon LD, Pauly M, et al. Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am J Physiol, Cell Physiol. 2015;308(9):C710-9.
Vainshtein, A., Tryon, L. D., Pauly, M., & Hood, D. A. (2015). Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. American Journal of Physiology. Cell Physiology, 308(9), pp. C710-9. doi:10.1152/ajpcell.00380.2014.
Vainshtein A, et al. Role of PGC-1α During Acute Exercise-induced Autophagy and Mitophagy in Skeletal Muscle. Am J Physiol, Cell Physiol. 2015 May 1;308(9):C710-9. PubMed PMID: 25673772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. AU - Vainshtein,Anna, AU - Tryon,Liam D, AU - Pauly,Marion, AU - Hood,David A, Y1 - 2015/02/11/ PY - 2014/12/02/received PY - 2015/02/04/accepted PY - 2015/2/13/entrez PY - 2015/2/13/pubmed PY - 2016/3/19/medline KW - Niemann-Pick C1 KW - biogenesis KW - endurance KW - mitochondria KW - physical activity SP - C710 EP - 9 JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. VL - 308 IS - 9 N2 - Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α. SN - 1522-1563 UR - https://www.unboundmedicine.com/medline/citation/25673772/Role_of_PGC_1α_during_acute_exercise_induced_autophagy_and_mitophagy_in_skeletal_muscle_ L2 - http://www.physiology.org/doi/full/10.1152/ajpcell.00380.2014?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -