| First Author | Vainshtein A | Year | 2015 |
| Journal | Am J Physiol Cell Physiol | Volume | 308 |
| Issue | 9 | Pages | C710-9 |
| PubMed ID | 25673772 | Mgi Jnum | J:224008 |
| Mgi Id | MGI:5661095 | Doi | 10.1152/ajpcell.00380.2014 |
| Citation | Vainshtein A, et al. (2015) Role of PGC-1alpha during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am J Physiol Cell Physiol 308(9):C710-9 |
| abstractText | 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-gamma coactivator-1alpha (PGC-1alpha). 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-1alpha 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-1alpha knockout (KO) animals. Deletion of PGC-1alpha 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-1alpha. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1alpha 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-1alpha. |
