Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise.
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.
Cartoni
Romain
R
Clinique Romande de Réadaptation, SUVACare, 1951 Sion, Switzerland.
Léger
Bertrand
B
Hock
M Benjamin
MB
Praz
Manu
M
Crettenand
Antoinette
A
Pich
Sara
S
Ziltener
Jean-Luc
JL
Luthi
François
F
Dériaz
Olivier
O
Zorzano
Antonio
A
Gobelet
Charles
C
Kralli
Anastasia
A
Russell
Aaron P
AP
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
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