Document Detail


AMPK is required for exercise-induced PGC-1α translocation to subsarcolemmal mitochondria in skeletal muscle.
MedLine Citation:
PMID:  23297307     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In skeletal muscle, mitochondria exist as two sub-cellular 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 PGC-1α and mitochondrial transcription factor A (Tfam) have been implicated in the direct regulation of the mitochondrial genome in mice, however SS and IMF differences may exist, and the potential signaling events regulating the mitochondrial content of these proteins has not been elucidated. Therefore, we examined the potential for PGC-1α and Tfam to translocate to SS and IMF mitochondria in human subjects, and performed experiments in rodents to identify signaling mechanisms regulating these translocation events. Acute exercise in humans and rats increased PGC-1α content in SS, but not IMF mitochondria. Acute exposure to AICAR in rats recapitulated the exercise effect of increased PGC-1α protein within SS mitochondria only, suggesting AMPK signaling is involved. In addition, rendering AMPK inactive (AMPK kinase dead mice) prevented exercise-induced PGC-1α translocation to SS mitochondria, further suggesting that AMPK plays an integral role in these translocation events. In contrast to the conserved PGC-1α translocation to SS mitochondria across species (humans, rats and mice), acute exercise only increased mitochondrial Tfam in rats. Nevertheless, in rat resting muscle PGC-1α and Tfam co-immunoprecipate with α-tubulin suggesting a common cytosolic localization. These data suggest that exercise causes translocation of PGC-1α preferentially to SS mitochondria in an AMPK dependent manner.
Authors:
Brennan K Smith; Kazutaka Mukai; James S Lally; Amy C Maher; Brendon J Gurd; George J F Heigenhauser; Lawrence L Spriet; Graham P Holloway
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-7
Journal Detail:
Title:  The Journal of physiology     Volume:  -     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Guelph;
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