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.
Highlights
Introduction(PGC-1␣) is regarded as a crucial regulator of mitochondrial biogenesis by virtue of its ability to co-activate and augment the functions as a transcriptional co-activator for both nuclear expression and activity of several transcription factors that in and mitochondrial DNA transcription factors
In this study we confirmed that PGC-1␣, which has long been considered a nuclear specific transcription co-activator regulating transcription of nuclear DNA-encoded mitochondrial genes [6], localizes in mitochondria purified from C67Bl/6J mouse skeletal muscle
Mitochondrial PGC-1␣ is primarily localized in the mitochondrial matrix where it forms a complex with Tfam only when Tfam is bound to the mitochondrial DNA (mtDNA) D-loop region
Summary
(PGC-1␣) is regarded as a crucial regulator of mitochondrial biogenesis by virtue of its ability to co-activate and augment the functions as a transcriptional co-activator for both nuclear expression and activity of several transcription factors that in and mitochondrial DNA transcription factors. These results turn bind to the promoters of distinct sets of nuclear-encoded suggest that PGC-1␣ may dynamically facilitate nuclear-mi- mitochondrial genes [6, 8]. Transcription via increased expression of mitochondrial transcription factor A (Tfam) as executed by its co-activation of nuclear respiratory factor 1 (NRF-1) (9 –11). Doctoral Research Scholarship and the Canada PRESTIGE Fellowship. 2 Funded by Natural Sciences and Engineering Research Council of Canada
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
