EXERCISE- INDUCED MITOCHONDRIAL ADAPTATIONS AND THEIR ROLE IN PREVENTIVE MEDICINE

Julia Lorek; Patrycja  Waszkiewicz; Magda Sawin; Katarzyna Szeliga; Wiktoria Brzozowska; Daniel Grobecki; Franciszek Jabłoński; Hanna Jabłońska; Jakub Korybski; Adam Jarczak

doi:10.31435/ijitss.3(51).2026.5880

Authors

Julia Lorek Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0000-4738-074X
Patrycja Waszkiewicz Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0000-2403-705X
Magda Sawin Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0003-7893-804X
Katarzyna Szeliga Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0005-3006-2178
Wiktoria Brzozowska Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0005-3615-8023
Daniel Grobecki Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0005-1724-7784
Franciszek Jabłoński Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0006-3715-1429
Hanna Jabłońska Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0001-0849-7352
Jakub Korybski Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0006-4499-3149
Adam Jarczak Wrocław University Hospital, Borowska 213, 50-556 Wrocław, Poland https://orcid.org/0009-0008-0801-0058

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.5880

Keywords:

Mitochondrial Biogenesis, Exercise Training, Mitochondrial Dynamics, Cardiovascular Disease, Metabolic Health, Preventive Medicine

Abstract

Background. Mitochondrial dysfunction is a key mechanism underlying chronic diseases such as type 2 diabetes, cardiovascular disease, neurodegenerative disorders, and age-related conditions. In contrast, exercise training promotes mitochondrial adaptations that improve metabolic health and physical performance, making mitochondrial health an important therapeutic target.

Aim. The aim of this review was to evaluate the current evidence on exercise-induced mitochondrial adaptations and their role in disease prevention, focusing on molecular mechanisms linking sports science with preventive medicine.

Materials and Methods. A literature review was conducted using PubMed, Web of Science, and SPORTDiscus databases. Studies published between 2019 and 2026 were selected according to predefined inclusion and exclusion criteria and analyzed qualitatively.

Results. Evidence shows that exercise training increases skeletal muscle mitochondrial content and activates pathways regulating biogenesis, dynamics, and quality control. These adaptations also occur in vascular, cardiac, and neural tissues, enhancing oxidative capacity, metabolic flexibility, and antioxidant defense, particularly in type 2 diabetes prevention. However, differences in exercise protocols and outcome measures limit conclusions regarding optimal training prescriptions.

Conclusions. Mitochondrial adaptations are a major mechanism linking exercise to disease prevention. Different exercise modalities induce distinct mitochondrial responses, supporting precision exercise prescription in athletic and clinical populations.

References

Mølmen, K. S., Almquist, N. W., & Skattebo, Ø. (2025). Effects of exercise training on mitochondrial and capillary growth in human skeletal muscle: A systematic review and meta-regression. Sports Med, 55(1), 115–144. https://doi.org/10.1007/s40279-024-02120-2

Memme, J. M., Erlich, A. T., Phukan, G., & Hood, D. A. (2021). Exercise and mitochondrial health. J Physiol, 599(3), 803–817. https://doi.org/10.1113/JP278853

Nayor, M., Shah, S. H., Murthy, V., & Shah, R. V. (2021). Molecular aspects of lifestyle and environmental effects in patients with diabetes: JACC focus seminar. J Am Coll Cardiol, 78(5), 481–495. https://doi.org/10.1016/j.jacc.2021.02.070

Ruegsegger, G. N., Pataky, M. W., Simha, S., et al. (2023). High-intensity aerobic, but not resistance or combined, exercise training improves both cardiometabolic health and skeletal muscle mitochondrial dynamics. J Appl Physiol, 135(4), 763–774. https://doi.org/10.1152/japplphysiol.00405.2023

Zhang, X., & Gao, F. (2021). Exercise improves vascular health: Role of mitochondria. Free Radic Biol Med, 177, 347–359. https://doi.org/10.1016/j.freeradbiomed.2021.11.002

Han, C., Lu, P., & Yan, S. Z. (2022). Effects of high-intensity interval training on mitochondrial supercomplex assembly and biogenesis, mitophagy, and the AMP-activated protein kinase pathway in the soleus muscle of aged female rats. Exp Gerontol, 158, 111648. https://doi.org/10.1016/j.exger.2021.111648

Batterson, P. M., McGowan, E. M., Stierwalt, H. D., et al. (2023). Two weeks of high-intensity interval training increases skeletal muscle mitochondrial respiration via complex-specific remodeling in sedentary humans. J Appl Physiol, 134(2), 339–355. https://doi.org/10.1152/japplphysiol.00467.2022

Botella, J., Schytz, C. T., Pehrson, T. F., et al. (2023). Increased mitochondrial surface area and cristae density in the skeletal muscle of strength athletes. J Physiol, 601(14), 2899–2915. https://doi.org/10.1113/JP284394

Diaz-Vegas, A., Sanchez-Aguilera, P., Krycer, J. R., et al. (2020). Is mitochondrial dysfunction a common root of noncommunicable chronic diseases? Endocr Rev, 41(3), bnaa005. https://doi.org/10.1210/endrev/bnaa005

Feng, L., Li, B., Yong, S. S., Wen, X., & Tian, Z. (2024). The emerging role of exercise in Alzheimer's disease: Focus on mitochondrial function. Ageing Res Rev, 101, 102486. https://doi.org/10.1016/j.arr.2024.102486

Vabishchevich, V., Smith, R. T., & Bittel, A. J. (2026). Markers of clinical and mitochondrial adaptation in response to moderate intensity continuous training: A systematic review and meta-analysis. PLoS One, 21(1), e0339902. https://doi.org/10.1371/journal.pone.0339902

Chaput, J. P., Willumsen, J., Bull, F., et al. (2020). 2020 WHO guidelines on physical activity and sedentary behaviour for children and adolescents aged 5-17 years: Summary of the evidence. Int J Behav Nutr Phys Act, 17(1), 141. https://doi.org/10.1186/s12966-020-01037-z

McCoin, C. S., Franczak, E., Deng, F., et al. (2022). Acute exercise rapidly activates hepatic mitophagic flux. J Appl Physiol, 132(3), 862–873. https://doi.org/10.1152/japplphysiol.00704.2021

Chen, M., Zhu, J. Y., Mu, W. J., et al. (2023). Cdo1-Camkk2-Ampk axis confers the protective effects of exercise against NAFLD in mice. Nat Commun, 14(1), 8391. https://doi.org/10.1038/s41467-023-44242-7

Bórquez, J. C., Díaz-Castro, F., La Fuente, F. P., et al. (2023). Mitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD. Metabolism, 155765. https://doi.org/10.1016/j.metabol.2023.155765

Zhao, N., Zhang, X., Li, B., et al. (2023). Treadmill exercise improves PINK1/Parkin-mediated mitophagy activity against Alzheimer's disease pathologies by upregulated SIRT1-FOXO1/3 axis in APP/PS1 mice. Mol Neurobiol, 60(1), 277–291. https://doi.org/10.1007/s12035-022-03035-7

Zhao, N., Yan, Q. W., Xia, J., et al. (2020). Treadmill exercise attenuates Aβ-induced mitochondrial dysfunction and enhances mitophagy activity in APP/PS1 transgenic mice. Neurochem Res, 45(5), 1202–1214. https://doi.org/10.1007/s11064-020-03003-4

Zhao, X., Huang, F., Sun, Y., & Li, L. (2025). Mechanisms of endurance and resistance exercise in type 2 diabetes mellitus: A narrative review. Biochem Biophys Res Commun, 761, 151731. https://doi.org/10.1016/j.bbrc.2025.151731

Zhu, W., Zhou, Z., Sun, J., & Si, J. (2025). Effects of exercise training on skeletal muscle mitochondrial outcomes in type 2 diabetes: A systematic review and meta-analysis. Front Physiol, 16, 1671926. https://doi.org/10.3389/fphys.2025.1671926

Greggio, C., Jha, P., Kulkarni, S. S., et al. (2017). Enhanced respiratory chain supercomplex formation in response to exercise in human skeletal muscle. Cell Metab, 25(2), 301–311. https://doi.org/10.1016/j.cmet.2016.11.004

Wang, C. H., & Wei, Y. H. (2017). Role of mitochondrial dysfunction and dysregulation of ca homeostasis in the pathophysiology of insulin resistance and type 2 diabetes. J Biomed Sci, 24(1), 70. https://doi.org/10.1186/s12929-017-0375-3

Prasun, P. (2020). Mitochondrial dysfunction in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis, 1866(10), 165838. https://doi.org/10.1016/j.bbadis.2020.165838

Atici, A. E., Crother, T. R., & Noval Rivas, M. (2023). Mitochondrial quality control in health and cardiovascular diseases. Front Cell Dev Biol, 11, 1290046. https://doi.org/10.3389/fcell.2023.1290046

Dent, J. R., Stocks, B., Campelj, D. G., & Philp, A. (2023). Transient changes to metabolic homeostasis initiate mitochondrial adaptation to endurance exercise. Semin Cell Dev Biol, 143, 3–16. https://doi.org/10.1016/j.semcdb.2022.03.022

Ringholm, S., Gudiksen, A., Frey Halling, J., et al. (2023). Impact of aging and lifelong exercise training on mitochondrial function and network connectivity in human skeletal muscle. J Gerontol A Biol Sci Med Sci, 78(3), 373–383. https://doi.org/10.1093/gerona/glac164

Porter, C., Reidy, P. T., Bhattarai, N., Sidossis, L. S., & Rasmussen, B. B. (2015). Resistance exercise training alters mitochondrial function in human skeletal muscle. Med Sci Sports Exerc, 47(9), 1922–1931. https://doi.org/10.1249/MSS.0000000000000605

Slavin, M. B., Memme, J. M., Oliveira, A. N., Moradi, N., & Hood, D. A. (2022). Regulatory networks coordinating mitochondrial quality control in skeletal muscle. Am J Physiol Cell Physiol, 322(5), C913–C926. https://doi.org/10.1152/ajpcell.00065.2022

Botella, J., Perri, E., Caruana, N. J., et al. (2025). Sprint interval exercise disrupts mitochondrial ultrastructure driving a unique mitochondrial stress response and remodelling in men. Nat Commun, 17(1), 71. https://doi.org/10.1038/s41467-025-66625-8

Xia, D., Liu, Y., Wu, P., & Wei, D. (2023). Current advances of mitochondrial dysfunction and cardiovascular disease and promising therapeutic strategies. Am J Pathol, 193(10), 1485–1500. https://doi.org/10.1016/j.ajpath.2023.06.013

Tucker, W. J., Fegers-Wustrow, I., Halle, M., et al. (2022). Exercise for primary and secondary prevention of cardiovascular disease: JACC focus seminar 1/4. J Am Coll Cardiol, 80(11), 1091–1106. https://doi.org/10.1016/j.jacc.2022.07.004

van der Ploeg, H. P., & Bull, F. C. (2020). Invest in physical activity to protect and promote health: The 2020 WHO guidelines on physical activity and sedentary behaviour. Int J Behav Nutr Phys Act, 17(1), 145. https://doi.org/10.1186/s12966-020-01051-1

Clemente-Suárez, V. J., Martín-Rodríguez, A., Redondo-Flórez, L., et al. (2023). Metabolic health, mitochondrial fitness, physical activity, and cancer. Cancers (Basel), 15(3), 814. https://doi.org/10.3390/cancers15030814

Fang, E. F., Hou, Y., Palikaras, K., et al. (2019). Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nat Neurosci, 22(3), 401–412. https://doi.org/10.1038/s41593-018-0332-9

Liu, L., Deng, Z., Fang, R., et al. (2026). Exercise and CD8+ T cells: Mechanisms of immune modulation in antitumor responses. J Mol Med (Berl), 104(1), 54. https://doi.org/10.1007/s00109-026-02659-9

Sangwung, P., Petersen, K. F., Shulman, G. I., & Knowles, J. W. (2020). Mitochondrial dysfunction, insulin resistance, and potential genetic implications. Endocrinology, 161(4), bqaa017. https://doi.org/10.1210/endocr/bqaa017

Chen, J., Li, Y., Wang, L., & Liu, Q. (2025). The molecular mechanisms of exercise in cancer prevention and management. Eur J Cancer Prev, 34(4), 267–279. https://doi.org/10.1097/CEJ.0000000000000989