Mitochondrial DNA and Exercise: Implications for Health and Injuries in Sports
Open accessAbstract
Recently, several studies have highlighted the tight connection between mitochondria and physical activity. Mitochondrial functions are important in high-demanding metabolic activities, such as endurance sports. Moreover, regular training positively affects metabolic health by increasing mitochondrial oxidative capacity and regulating glucose metabolism. Exercise could have multiple effects, also on the mitochondrial DNA (mtDNA) and vice versa; some studies have investigated how mtDNA polymorphisms can affect the performance of general athletes and mtDNA haplogroups seem to be related to the performance of elite endurance athletes. Along with several stimuli, including pathogens, stress, trauma, and reactive oxygen species, acute and intense exercise also seem to be responsible for mtDNA release into the cytoplasm and extracellular space, leading to the activation of the innate immune response. In addition, several sports are characterized by a higher frequency of injuries, including cranial trauma, associated with neurological consequences. However, with regular exercise, circulating cell-free mtDNA levels are kept low, perhaps promoting cf-mtDNA removal, acting as a protective factor against inflammation.
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Regular physical activity or exercise training enhances mitochondrial homeostasis in individuals with sarcopenia and regulates mitophagy, mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial redox biology.
“Engaging in regular physical activity or exercise training, which proves beneficial for enhancing mitochondrial homeostasis in individuals with sarcopenia, significantly regulates mitophagy, mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial redox biology [9,10,11].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [11]
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Recreational scuba diving: negative or positive effects of oxidative and cardiovascular stress?
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Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise
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The toll of the gridiron: damage‐associated molecular patterns and hypertension in American football
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Decreased Circulating mtDNA Levels in Professional Male Volleyball Players
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Self-citationMitochondrial DNA Haplogroups and Highly Active Antiretroviral Therapy–Related Lipodystrophy
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Self-citationExercise intensity inferred from air consumption during recreational scuba diving.
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Self-citationMicroglia activation: a role for mitochondrial DNA?
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Self-citationMitochondrial DNA: a proinflammatory ‘enemy from within’ during HIV infection?
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Is mitochondrial DNA profiling predictive for athletic performance?
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Effects of whole-body cryotherapy on the innate and adaptive immune response in cyclists and runners
Nasi, M., Bianchini, E., Tartaro, D. L., Biasi, S. D., Mattioli, M., Paolini, A., Gibellini, L., Pinti, M., Gaetano, A. D., D’alisera, R., et al. (2020) · Immunologic Research · doi:10.1007/s12026-020-09165-1 · Cited by 14 · see citing works
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Vascular “Long COVID”: A New Vessel Disease?
Zanini, G., Selleri, V., Roncati, L., Coppi, F., Nasi, M., Farinetti, A., Manenti, A., Pinti, M., & Mattioli, A. V. (2023) · Angiology · doi:10.1177/00033197231153204 · Cited by 66 · see citing works
Self-citationTripathi, A., Bartosh, A., Whitehead, C., & Pillai, A. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02189-7 · Cited by 46 · see citing works
Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction
Jia, D., Tian, Z., & Wang, R. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102087 · Cited by 47 · see citing works
Genetic Profile in Genes Associated with Sports Injuries in Elite Endurance Athletes
Varillas‐Delgado, D., Gutiérrez‐Hellín, J., & Maestro, A. (2022) · International Journal of Sports Medicine · doi:10.1055/a-1917-9212 · Cited by 41 · see citing works
Perspectives on mitochondrial dysfunction in the regeneration of aging skeletal muscle
Wang, K., Gan, M., Lei, Y., Liao, T., Li, J., Niu, L., Zhao, Y., Chen, L., Wang, Y., Zhu, L., et al. (2025) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-025-00771-1 · Cited by 33 · see citing works
Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis
Wang, J., Jia, D., Zhang, Z., & Wang, D. (2025) · Metabolites · doi:10.3390/metabo15010059 · Cited by 23 · see citing works
CHCHD4-TRIAP1 regulation of innate immune signaling mediates skeletal muscle adaptation to exercise
Ma, J., Wang, P., Zhuang, J., Son, A. Y., Karius, A. K., Syed, A. M., Nishi, M., Wu, Z., Mori, M. P., Kim, Y., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113626 · Cited by 21 · see citing works
Innate immunity changes in soccer players after whole-body cryotherapy
Selleri, V., Mattioli, M., Tartaro, D. L., Paolini, A., Zanini, G., Gaetano, A. D., D’alisera, R., Roli, L., Melegari, A., Latessa, P. M., et al. (2022) · BMC Sports Science Medicine and Rehabilitation · doi:10.1186/s13102-022-00578-z · Cited by 13 · see citing works
Self-citationMastrototaro, L., & Roden, M. (2023) · PROTEOMICS · doi:10.1002/pmic.202300078 · Cited by 12 · see citing works
Yao, J., Saraf, F., Rathore, V. S., Darkazanli, K., Liu, Y., Korivi, M., & Bhaskar, L. V. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1568334 · Cited by 8 · see citing works
Cardiovascular Effects of Whole-Body Cryotherapy in Non-professional Athletes
Coppi, F., Pinti, M., Selleri, V., Zanini, G., D’alisera, R., Latessa, P. M., Tripi, F., Savino, G., Cossarizza, A., Nasi, M., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.905790 · Cited by 7 · see citing works
Self-citationMitochondrial innate immune signaling in skeletal muscle adaptation to exercise
Ma, J., Son, A. Y., Son, Y., Wang, P., & Hwang, P. M. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.05.004 · Cited by 6 · see citing works
Increase of circulating cell free mitochondrial DNA in amateur boxers after sparring matches
Selleri, V., Malerba, M., D’alisera, R., Seidenari, C., Sinigaglia, G., Zanini, G., Micheloni, G., Savino, G., Mattioli, A. V., Curia, G., et al. (2025) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2025.01.011 · Cited by 6 · see citing works
Self-citationExercise as elixir to combat cardiovascular ageing
Feng, Z., Yuan, X., Yi, W., Gao, F., Sun, Y., & Zhang, X. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102848 · Cited by 5 · see citing works
The Impact of COVID-19 Infection on Abdominal Aortic Aneurysms: Mechanisms and Clinical Implications
Cao, Z., Gao, J., Wu, J.-Q., & Zheng, Y.-H. (2024) · Cardiovascular Therapeutics · doi:10.1155/2024/7288798 · Cited by 5 · see citing works
Pedriali, G., Leo, S., Tiezzi, M., Colarusso, E. N., Morciano, G., Tremoli, E., & Pinton, P. (2026) · Basic Research in Cardiology · doi:10.1007/s00395-026-01162-z · Cited by 4 · see citing works
Gao, J., Li, L., Zhai, S., Dong, Y., Zhang, Z., Lin, D., & Ma, J. (2025) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2025.5632 · Cited by 2 · see citing works
Tomaskovic, A., Strepp, T., STÖGGL, T. L., Neuberger, E. W. I., Simon, P. D., & Haller, N. (2025) · Sports Medicine - Open · doi:10.1186/s40798-025-00923-9 · Cited by 2 · see citing works
Demi̇r, R. (2023) · doi:10.5152/0114 · Cited by 2 · see citing works
Caffeine and cardiovascular aging: exploring sex-specific impacts on risk and arrhythmias
Farinetti, A., Manenti, A., Cocchi, C., & Mattioli, A. V. (2025) · 老年心脏病学杂志：英文版 · doi:10.26599/1671-5411.2025.08.001 · Cited by 1 · see citing works
Self-citationImpact of exercise-induced DNA damage repair on age-related muscle weakness and sarcopenia
朱, 玲., Su, Y., & Su, Z. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2025.1639224 · Cited by 1 · see citing works
Selleri, V., Bazo, M., Sinigaglia, G., Zanini, G., Micheloni, G., Coppi, F., D’alisera, R., Savino, G., Nasi, M., & Pinti, M. (2026) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2026.03.024 · Cited by 1 · see citing works
Self-citationKiiskilä, J., Hassinen, I. E., Kettunen, J., Kytövuori, L., Mikkola, I., Härkönen, P. K., Jokelainen, J. J., Keinanen-Kiukaanniemi, S. M., Perola, M., & Majamaa, K. (2022) · BMC Sports Science Medicine and Rehabilitation · doi:10.1186/s13102-022-00485-3
Effect of Noninvasive Static Human Data on Maximum Data in Exercise
Wu, Y., & Sun, Y. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20021612
Multiparametric analysis of tumor infiltrating lymphocytes in solid tumors
Borella, R., Paolini, A., Aramini, B., Gibellini, L., Masciale, V., Tartaro, D. L., Dominici, M., Biasi, S. D., & Cossarizza, A. (2023) · Methods in cell biology · doi:10.1016/bs.mcb.2023.03.006
Self-citationKalp Kapak Hastalıkları ve Spor Kardiyolojisi
Özyıldırım, S. (2023) · doi:10.5152/0105
Ritim Bozuklukları ve Spor Kardiyolojisi
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Perikardit ve Spor Kardiyolojisi
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Fonksiyonel Tıp ve Spor İlişkisi
Yıldız, M. (2023) · doi:10.5152/0113
Altan, M. (2023) · doi:10.5152/0102
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Si̇nan, Ü. Y. (2023) · doi:10.5152/0104
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The Investigation of Relationship Between Sporting Performance and Mitochondria and Genes
KAHYA, S. (2024) · Yalova Üniversitesi spor bilimleri dergisi. · doi:10.70007/yalovaspor.1509439
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Self-citationChanges in the proteomic profile of athletes’ plasma associated with exercise intensity
Malsagova, K. A., Butkova, T. V., Nikolsky, K. S., Petrovskiy, D. V., Kopylov, A. T., Игоревна, Н. В., Kulikova, L. I., Rudnev, V. R., Yurku, K. A., Balakin, E. I., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-44729-5
Zhang, L., Xiaoyu, H., Zhang, J., Xiangyue, S., Zuo, H., Qun, W., & Gong, W. (2026) · iScience · doi:10.1016/j.isci.2026.117170
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- Authors
- Zanini, G., De Gaetano, A., Selleri, V., Savino, G., Cossarizza, A., Pinti, M., Mattioli, A. V., & Nasi, M.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
- Department of Public Healthcare, Sports Medicine Service, Azienda USL of Modena, 41121 Modena, Italy
- Corresponding author
- Nasi, Milena
- ORCID
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2021-09-28
- Volume
- 10
- Issue
- 10
- Pages
- 2575
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC8533813
- OpenAlex
- W3202334265
- Cited by
- 46
- References
- 117
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 3 · 2023: 22 · 2022: 4
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- mitochondrial DNA, physical activity, endurance athletes, mtDNA polymorphisms, mtDNA haplogroups, oxidative capacity, glucose metabolism, innate immune response, reactive oxygen species, sports injuries, cranial trauma, neuroinflammation, inflammation
- MeSH terms
- Athletic Injuries, DNA, Mitochondrial, Humans, Exercise
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