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Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise
Author(s) -
Cartoni Romain,
Léger Bertrand,
Hock M. Benjamin,
Praz Manu,
Crettenand Antoinette,
Pich Sara,
Ziltener JeanLuc,
Luthi François,
Dériaz Olivier,
Zorzano Antonio,
Gobelet Charles,
Kralli Anastasia,
Russell Aaron P.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.092031
Subject(s) - mfn2 , mfn1 , mitochondrial biogenesis , mitochondrial fusion , mitochondrion , microbiology and biotechnology , oxidative phosphorylation , biology , skeletal muscle , mitochondrial dna , endocrinology , gene , biochemistry
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.