| First Author | Smith BK | Year | 2013 |
| Journal | J Physiol | Volume | 591 |
| Issue | 6 | Pages | 1551-61 |
| PubMed ID | 23297307 | Mgi Jnum | J:207954 |
| Mgi Id | MGI:5559978 | Doi | 10.1113/jphysiol.2012.245944 |
| Citation | Smith BK, et al. (2013) AMP-activated protein kinase is required for exercise-induced peroxisome proliferator-activated receptor co-activator 1 translocation to subsarcolemmal mitochondria in skeletal muscle. J Physiol 591(Pt 6):1551-61 |
| abstractText | In skeletal muscle, mitochondria exist as two subcellular populations known as subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS mitochondria preferentially respond to exercise training, suggesting divergent transcriptional control of the mitochondrial genomes. The transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) and mitochondrial transcription factor A (Tfam) have been implicated in the direct regulation of the mitochondrial genome in mice, although SS and IMF differences may exist, and the potential signalling events regulating the mitochondrial content of these proteins have not been elucidated. Therefore, we examined the potential for PGC-1alpha and Tfam to translocate to SS and IMF mitochondria in human subjects, and performed experiments in rodents to identify signalling mechanisms regulating these translocation events. Acute exercise in humans and rats increased PGC-1alpha content in SS but not IMF mitochondria. Acute exposure to 5-aminoimidazole-4-carboxamide-1-beta-ribofuranoside in rats recapitulated the exercise effect of increased PGC-1alpha protein within SS mitochondria only, suggesting that AMP-activated protein kinase (AMPK) signalling is involved. In addition, rendering AMPK inactive (AMPK kinase dead mice) prevented exercise-induced PGC-1alpha translocation to SS mitochondria, further suggesting that AMPK plays an integral role in these translocation events. In contrast to the conserved PGC-1alpha translocation to SS mitochondria across species (humans, rats and mice), acute exercise only increased mitochondrial Tfam in rats. Nevertheless, in rat resting muscle PGC-1alpha and Tfam co-immunoprecipate with alpha-tubulin, suggesting a common cytosolic localization. These data suggest that exercise causes translocation of PGC-1alpha preferentially to SS mitochondria in an AMPK-dependent manner. |
