Mitofusins 1/2 and ERRα 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.
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Conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans.
“conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans (Cartoni et al., 2005; Dolinsky et al., 2013; Soriano et al., 2006).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Cartoni et al., 2005
PGC-1α and its downstream target gene product, ERRα, stimulate the expression of Mfn2.
“PGC-1α and its downstream target gene product, estrogen-related receptor-α (ERRα), stimulate the expression of Mfn2 (Cartoni et al., 2005; Soriano et al., 2006).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Cartoni et al., 2005
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- Authors
- Cartoni, R., Léger, B., Hock, M. B., Praz, M., Crettenand, A., Pich, S., Ziltener, J., Luthi, F., Dériaz, O., Zorzano, A., Gobelet, C., Kralli, A., & Russell, A. P.
- Affiliations
- Clinique Romande de Réadaptation (CH)
- Scripps Research Institute (US)
- Parc Científic de Barcelona (ES)
- Corresponding author
- Russell, Aaron P.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2005-08
- Volume
- 567
- Issue
- 1
- Pages
- 349-358
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- OpenAlex
- W2135645000
- Semantic Scholar
- 6bbf96698c77ef52f3721598083063b973181316
- Cited by
- 406
- References
- 38
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 10 · 2023: 20 · 2022: 23 · 2021: 12 · 2020: 24 · 2019: 19 · 2018: 26 · 2017: 28 · 2016: 28 · 2015: 31 · 2014: 19 · 2013: 31 · 2012: 22
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064951, DK 064951)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitofusins, Mfn1, mitofusin 2, estrogen-related receptor alpha, PGC-1α, skeletal muscle, physical activity, mitochondrial biogenesis, mitochondrial fusion, mitochondrial architecture, oxidative phosphorylation, Nrf2, cytochrome c oxidase subunit IV, insulin resistance, aerobic exercise
- MeSH terms
- Adult, Energy Metabolism, Humans, Male, Membrane Proteins, Mitochondria, Promoter Regions, Genetic, Signal Transduction, Exercise, Gene Expression, Muscle, Skeletal, GTP Phosphohydrolases, Mitochondrial Proteins, Membrane Transport Proteins, Mitochondrial Membrane Transport Proteins, Estrogen Receptor alpha
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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