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Mitofusions1/2 and ERRα expression are increased in human skeletal muscle after physical exercise.

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journal contribution
posted on 01.01.2005, 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 Russell
Mitochondrial 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 physiology

Volume

567

Issue

1

Pagination

349 - 358

Publisher

Cambridge University Press

Location

London, England

ISSN

0022-3751

eISSN

1469-7793

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, The Physiological Society