title: Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise.
abstract: 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-1alpha, NRF-1, NRF-2 and the recently implicated ERRalpha. We show that Mfn1, Mfn2, NRF-2 and COX IV mRNA were increased 24 h post-exercise, while PGC-1alpha and ERRalpha mRNA increased 2 h post-exercise. Finally, using in vitro cellular assays, we demonstrate that Mfn2 gene expression is driven by a PGC-1alpha programme dependent on ERRalpha. The PGC-1alpha/ERRalpha-mediated induction of Mfn2 suggests a role of these two factors in mitochondrial fusion. Our results provide evidence that PGC-1alpha not only mediates the increased expression of oxidative phosphorylation genes but also mediates alterations in mitochondrial architecture in response to aerobic exercise in humans.
authors.affiliation: Clinique Romande de Réadaptation, SUVACare, 1951 Sion, Switzerland.
authors.forename: Romain
authors.initials: R
authors.lastname: Cartoni
authors.forename: Bertrand
authors.initials: B
authors.lastname: Léger
authors.forename: M Benjamin
authors.initials: MB
authors.lastname: Hock
authors.forename: Manu
authors.initials: M
authors.lastname: Praz
authors.forename: Antoinette
authors.initials: A
authors.lastname: Crettenand
authors.forename: Sara
authors.initials: S
authors.lastname: Pich
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ziltener
authors.forename: François
authors.initials: F
authors.lastname: Luthi
authors.forename: Olivier
authors.initials: O
authors.lastname: Dériaz
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.forename: Charles
authors.initials: C
authors.lastname: Gobelet
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kralli
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
mesh_terms: D000328:Adult; D004734:Energy Metabolism / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D015444:Exercise / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics*; D008928:Mitochondria / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C470017:Mfn1 protein, human