The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle
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Objective Mitochondria are organelles primarily responsible for energy production, and recent evidence indicates that alterations in size, shape, location, and quantity occur in response to fluctuations in energy supply and demand. We tested the impact of acute and chronic exercise on mitochondrial dynamics signaling and determined the impact of the mitochondrial fission regulator Dynamin related protein (Drp)1 on exercise performance and muscle adaptations to training. Methods Wildtype and muscle-specific Drp1 heterozygote (mDrp1 +/− ) mice, as well as dysglycemic (DG) and healthy normoglycemic men (control) performed acute and chronic exercise. The Hybrid Mouse Diversity Panel, including 100 murine strains of recombinant inbred mice , was used to identify muscle Dnm1L (encodes Drp1)-gene relationships. Results Endurance exercise impacted all aspects of the mitochondrial life cycle , i.e. fission-fusion, biogenesis, and mitophagy . Dnm1L gene expression and Drp1 Ser616 phosphorylation were markedly increased by acute exercise and declined to baseline during post-exercise recovery. Dnm1L expression was strongly associated with transcripts known to regulate mitochondrial metabolism and adaptations to exercise. Exercise increased the expression of DNM1L in skeletal muscle of healthy control and DG subjects, despite a 15% ↓( P = 0.01) in muscle DNM1L expression in DG at baseline. To interrogate the role of Dnm1L further, we exercise trained male mDrp1 +/− mice and found that Drp1 deficiency reduced muscle endurance and running performance, and altered muscle adaptations in response to exercise training. Conclusion Our findings highlight the importance of mitochondrial dynamics, specifically Drp1 signaling, in the regulation of exercise performance and adaptations to endurance exercise training.
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There is strong evidence in skeletal muscle supporting a causal link between dysregulation of mitochondrial fission and alterations in muscle maintenance.
“There is strong evidence in skeletal muscle that supports a causal link between the dysregulation of mitochondrial fission and alterations in muscle maintenance [152, 196, 197, 210, 211].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [211]
Another study using muscle-specific DRP1 heterozygote mice showed reduced muscle endurance and running performance, and altered muscle adaptations in response to exercise training.
“Another study using muscle-specific DRP1 heterozygote mice showed reduced muscle endurance and running performance, and altered muscle adaptations in response to exercise training [211].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [211]
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- Authors
- Moore, T. M., Zhou, Z., Cohn, W., Norheim, F., Lin, A. J., Kalajian, N., Strumwasser, A. R., Cory, K., Whitney, K., Ho, T., Ho, T., Lee, J. L., Rucker, D. H., Shirihai, O., van der Bliek, A. M., Whitelegge, J. P., Seldin, M. M., Lusis, A. J., Lee, S., Drevon, C. A., Mahata, S. K., Turcotte, L. P., & Hevener, A. L.
- Affiliations
- University of Southern California (US)
- University of California, Los Angeles (US)
- University of Oslo (NO)
- University of California San Diego (US)
- Corresponding author
- Hevener, Andrea L.
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 21
- Pages
- 51-67
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC6407367
- OpenAlex
- W2902937014
- Cited by
- 131
- References
- 79
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 14 · 2023: 17 · 2022: 17 · 2021: 16 · 2020: 22 · 2019: 9
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
- Funders
- Institute of Basic Medical Sciences
- National Institute on Aging (5P30AG028748)
- National Aeronautics and Space Administration
- Norges Forskningsråd
- American College of Sports Medicine
- National Institutes of Health (P30DK063491, U24DK097748, F31DK108657, DK109724, 5T32HD007228)
- U.S. Department of Veterans Affairs (NCT01803568, I01BX000323, HL28481, HL30568)
- Seventh Framework Programme (289511)
- Clinical and Translational Science Institute, University of California, Los Angeles (ULTR000124)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial dynamics, Drp1, mitochondrial fission, mitochondrial fusion, mitophagy, mitochondrial biogenesis, exercise training, endurance exercise, skeletal muscle, exercise performance, dysglycemia, Hybrid Mouse Diversity Panel, mitochondrial metabolism
- MeSH terms
- Physical Functional Performance, Adaptation, Physiological, Adult, Aged, Animals, Blood Glucose, Female, Humans, Male, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Microtubule-Associated Proteins, Middle Aged, Mitochondria, Phosphorylation, Physical Conditioning, Animal, Physical Endurance, Gene Deletion, Muscle, Skeletal, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, Mice, Mitochondrial Dynamics
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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