Over-Expressing Mitofusin-2 in Healthy Mature Mammalian Skeletal Muscle Does Not Alter Mitochondrial Bioenergetics
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The role of mitofusin-2 (MFN-2) in regulating mitochondrial dynamics has been well-characterized in lower order eukaryotic cell lines through the complete ablation of MFN-2 protein. However, to support the contractile function of mature skeletal muscle, the subcellular architecture and constituent proteins of this tissue differ substantially from simpler cellular organisms. Such differences may also impact the role of MFN-2 in mature mammalian muscle, and it is unclear if minor fluctuations in MFN-2, as observed in response to physiological perturbations, has a functional consequence. Therefore, we have transiently transfected MFN-2 cDNA into rat tibialis anterior muscle to determine the effect of physiolgically relevant increases in MFN-2 protein on mitochondrial bioenergetics. Permeabilized muscle fibres generated from muscle following MFN-2-transfection were used for functional assessments of mitochondrial bioenergetics. In addition, we have further established a novel method for selecting fibre bundles that are positively transfected, and using this approach transient transfection increased MFN-2 protein ∼2.3 fold in selected muscle fibres. However, this did not alter maximal rates of oxygen consumption or the sensitivity for ADP-stimulated respiration. In addition, MFN-2 over-expression did not alter rates of H(2)O(2) emission. Altogether, and contrary to evidence from lower order cell lines, our results indicate that over-expressing MFN-2 in healthy muscle does not influence mitochondrial bioenergetics in mature mammalian skeletal muscle.
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Modulation (overexpression or deletion) of proteins regulating mitochondrial dynamics in mice has either shown no benefit to muscle cells or was proven deleterious to muscle health.
“To date, the modulation (overexpression or deletion) of proteins regulating mitochondrial dynamics in mice has either shown no benefit to muscle cells [68] or was proven deleterious to muscle health (Drp1 overexpression, Drp1 knockout, Drp1 knockdown, and Mfn1+Mfn2 knockout).”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [68]
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References 44 · Cited by 19
- Authors
- Lally, J. S. V., Herbst, E. A. F., Matravadia, S., Maher, A. C., Perry, C. G. R., Ventura-Clapier, R., & Holloway, G. P.
- Affiliations
- University of Guelph (CA)
- Corresponding author
- Holloway, Graham P.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-31
- Volume
- 8
- Issue
- 1
- Pages
- e55660
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3561349
- OpenAlex
- W2083906680
- Cited by
- 19
- References
- 44
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 2
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitofusin 2, mitochondrial dynamics, mitochondrial bioenergetics, skeletal muscle, transient transfection, tibialis anterior, oxygen consumption, ADP-stimulated respiration, hydrogen peroxide emission
- MeSH terms
- Animals, Energy Metabolism, Female, Hydrogen Peroxide, Membrane Proteins, Mitochondria, Muscle, Transfection, Gene Expression, Muscle, Skeletal, Muscle Fibers, Skeletal, Cell Respiration, GTP Phosphohydrolases, Mitochondrial Proteins, Rats
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