n20062122.pdf (520.78 kB)
Mitofusions1/2 and ERRα expression are increased in human skeletal muscle after physical exercise.
journal contribution
posted on 2005-01-01, 00:00 authored by R Cartoni, B Leger, M Hock, M Praz, A Crettenand, S Pich, J L Ziltener, F Luthi, O Deriaz, A Zorzano, C Gobelet, A Kralli, Aaron RussellAaron RussellMitochondrial impairment is hypothesized to contribute to the pathogenesis of insulin resistance. Mitofusin (Mfn) proteins regulate the biogenesis and maintenance of the mitochondrial network, and when inactivated, cause a failure in the mitochondrial architecture and decreases in oxidative capacity and glucose oxidation. Exercise increases muscle mitochondrial content, size, oxidative capacity and aerobic glucose oxidation. To address if Mfn proteins are implicated in these exercise-induced responses, we measured Mfn1 and Mfn2 mRNA levels, pre-, post-, 2 and 24 h post-exercise. Additionally, we measured the expression levels of transcriptional regulators that control mitochondrial biogenesis and functions, including PGC-1α, NRF-1, NRF-2 and the recently implicated ERRα. We show that Mfn1, Mfn2, NRF-2 and COX IV mRNA were increased 24 h post-exercise, while PGC-1α and ERRα mRNA increased 2 h post-exercise. Finally, using in vitro cellular assays, we demonstrate that Mfn2 gene expression is driven by a PGC-1α programme dependent on ERRα. The PGC-1α/ERRα-mediated induction of Mfn2 suggests a role of these two factors in mitochondrial fusion. Our results provide evidence that PGC-1α not only mediates the increased expression of oxidative phosphorylation genes but also mediates alterations in mitochondrial architecture in response to aerobic exercise in humans.
History
Journal
Journal of physiologyVolume
567Issue
1Pagination
349 - 358Publisher
Cambridge University PressLocation
London, EnglandPublisher DOI
ISSN
0022-3751eISSN
1469-7793Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2005, The Physiological SocietyUsage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC