PMID:21245132

Citation	Safdar, A, Little, JP, Stokl, AJ, Hettinga, BP, Akhtar, M and Tarnopolsky, MA (2011) Exercise increases mitochondrial PGC-1alpha content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J. Biol. Chem. 286:10605-17
Abstract	Endurance exercise is known to induce metabolic adaptations in skeletal muscle via activation of the transcriptional co-activator peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α). PGC-1α regulates mitochondrial biogenesis via regulating transcription of nuclear-encoded mitochondrial genes. Recently, PGC-1α has been shown to reside in mitochondria; however, the physiological consequences of mitochondrial PGC-1α remain unknown. We sought to delineate if an acute bout of endurance exercise can mediate an increase in mitochondrial PGC-1α content where it may co-activate mitochondrial transcription factor A to promote mtDNA transcription. C57Bl/6J mice (n = 12/group; ♀ = ♂) 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-1α in END and END+3h groups was significantly higher versus SED mice. In mitochondria, PGC-1α 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-1α at the NRF-1 promoter. We conclude that in response to acute altered energy demands, PGC-1α 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-1α may dynamically facilitate nuclear-mitochondrial DNA cross-talk to promote net mitochondrial biogenesis.
Links	PubMed PMC3060512 Online version:10.1074/jbc.M110.211466
Keywords	Animals; Cell Nucleus/genetics; Cell Nucleus/metabolism; DNA, Mitochondrial/genetics; DNA, Mitochondrial/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Energy Metabolism/physiology; Female; Male; Mice; Mitochondria, Muscle/genetics; Mitochondria, Muscle/metabolism; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Nuclear Respiratory Factor 1/biosynthesis; Nuclear Respiratory Factor 1/genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Physical Conditioning, Animal; Physical Endurance/physiology; Promoter Regions, Genetic/physiology; Trans-Activators/biosynthesis; Trans-Activators/genetics; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CISY		GO:0005759: mitochondrial matrix	ECO:0000314:		C		As seen on figure 6, localization of CS (citrate synthase) can be seen to be to the Mitochondrial Matrix. Citrate synthase, mitochondrial Mouse	complete CACAO 12798
MOUSE:TOM22		GO:0005741: mitochondrial outer membrane	ECO:0000314:		C		As seen on figure 6, localization of TOM22 is to the outer mitochondrial membrane (OMM). Mitochondrial import receptor subunit TOM22 Mouse	complete CACAO 12796
MOUSE:TFAM		GO:0005759: mitochondrial matrix	ECO:0000314:		C		As seen on figure 6, Tfam is localized to the mitochondrial matrix. Transcription factor A, mitochondrial Mouse	complete CACAO 12797

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