期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 12, 页码 10605-10617出版社
ELSEVIER
DOI: 10.1074/jbc.M110.211466
关键词
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资金
- Canadian Institutes of Health Research [MOP97805]
- Warren Lammert and family
- Canadian Institutes of Health Research Institute of Aging
- Canada PRESTIGE Fellowship
- Natural Sciences and Engineering Research Council of Canada
Endurance exercise is known to induce metabolic adaptations in skeletal muscle via activation of the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha). PGC-1 alpha regulates mitochondrial biogenesis via regulating transcription of nuclear-encoded mitochondrial genes. Recently, PGC-1 alpha has been shown to reside in mitochondria; however, the physiological consequences of mitochondrial PGC-1 alpha remain unknown. We sought to delineate if an acute bout of endurance exercise can mediate an increase in mitochondrial PGC-1 alpha content where it may co-activate mitochondrial transcription factor A to promote mtDNA transcription. C57Bl/6J mice (n = 12/group; female = male) were randomly assigned to sedentary (SED), forced-endurance (END) exercise (15 m/min for 90 min), or forced endurance + 3 h of recovery (END + 3h) group. The END group was sacrificed immediately after exercise, whereas the SED and END + 3h groups were euthanized 3 h after acute exercise. Acute exercise coordinately increased the mRNA expression of nuclear and mitochondrial DNA-encoded mitochondrial transcripts. Nuclear and mitochondrial abundance of PGC-1 alpha in END and END + 3h groups was significantly higher versus SED mice. In mitochondria, PGC-1 alpha is in a complex with mitochondrial transcription factor A at mtDNA D-loop, and this interaction was positively modulated by exercise, similar to the increased binding of PGC-1 alpha at the NRF-1 promoter. We conclude that in response to acute altered energy demands, PGC-1 alpha re-localizes into nuclear and mitochondrial compartments where it functions as a transcriptional co-activator for both nuclear and mitochondrial DNA transcription factors. These results suggest that PGC-1 alpha may dynamically facilitate nuclear-mitochondrial DNA cross-talk to promote net mitochondrial biogenesis.
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