Cited by 247Cardiovascular and exercise physiologyMitochondrial Function and PathologyExercise and Physiological Responses

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Training-Induced Changes in Mitochondrial Content and Respiratory Function in Human Skeletal Muscle

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Granata, Cesare, Jamnick, Nicholas A., Bishop, David J.·2018·Sports Medicine

DOI 10.1007/s40279-018-0936-y

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Abstract

A sedentary lifestyle has been linked to a number of metabolic disorders that have been associated with sub-optimal mitochondrial characteristics and an increased risk of premature death. Endurance training can induce an increase in mitochondrial content and/or mitochondrial functional qualities, which are associated with improved health and well-being and longer life expectancy. It is therefore important to better define how manipulating key parameters of an endurance training intervention can influence the content and functionality of the mitochondrial pool. This review focuses on mitochondrial changes taking place following a series of exercise sessions (training-induced mitochondrial adaptations), providing an in-depth analysis of the effects of exercise intensity and training volume on changes in mitochondrial protein synthesis, mitochondrial content and mitochondrial respiratory function. We provide evidence that manipulation of different exercise training variables promotes specific and diverse mitochondrial adaptations. Specifically, we report that training volume may be a critical factor affecting changes in mitochondrial content, whereas relative exercise intensity is an important determinant of changes in mitochondrial respiratory function. As a consequence, a dissociation between training-induced changes in mitochondrial content and mitochondrial respiratory function is often observed. We also provide evidence that exercise-induced changes are not necessarily predictive of training-induced adaptations, we propose possible explanations for the above discrepancies and suggestions for future research.

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Self-citation
Treadmill training protects valproic acid-induced autistic features via cerebellar AMPK/PPAR-γ dependent pathway and improves mitochondrial activity in mice
Shaban, A. M., Ameen, O., Omar, M., Derbaly, S. A. E., Omara, H. R., Bayomi, A. I., Latif, A. A. A., Elakabawy, Z. I., & Khodir, S. A. (2025) · Scientific Reports · doi:10.1038/s41598-025-09089-6 · Cited by 6
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“However, it appears that training volume rather than exercise intensity is the most important determinant of exercise training- induced increases in mitochondrial content (Granata et al., 2018).”
Background
Disruption of neuromedin B receptor improves mitochondrial oxidative phosphorylation capacity in gastrocnemius muscle of female mice
Bento‐Bernardes, T., Rossetti, C. L., de Andrade, C. B. V., Souza, L. L., Wilieman, M., de Paula, G. S. M., Woyames, J., Oliveira, K. J., da‐Silva, W. S., & Pazos-Moura, C. C. (2022) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00073.2021 · Cited by 3
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“Likewise, the seminal work of Holloszy (1967) demonstrating that progressive aerobic exercise training elicits substantial mitochondrial biogenesis has been followed by an abundance of research over subsequent decades with similar findings (for review, see Granata et al., 2018).”
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Plasticity and evolved changes in mitochondrial physiology across skeletal muscles of high-altitude deer mice ( Peromyscus maniculatus )
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Influential
Chamber oxygen concentration impacts mitochondrial function and hydrogen peroxide appearance in permeabilized human skeletal muscle fibers
Ruple, B. A., Park, S. H., Craig, J. C., Lewis, M. T., Trinity, J. D., Richardson, R. S., & Broxterman, R. M. (2025) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2025.149568 · Cited by 1
“Researchers routinely assess mitochondrial respiration using high-resolution respirometry to reveal the effects of diseases [1–3], interventions [4–6], and substrate utilization [7,8] on skeletal muscle mitochondrial bioenergetics.”
Steepest near‐infrared spectroscopy‐derived deoxygenation slopes during arterial occlusions provide more reliable assessments of muscle mitochondrial capacity
Costalat, G., Sautillet, B., Millet, G. P., Unal, C., Abaïdia, A., Hassar, A., & Cozette, M. (2025) · Experimental Physiology · doi:10.1113/ep093040 · Cited by 1
Exercise induces sex-specific assembly of mitochondrial supercomplexes
Huertas, J. R., Aragón‐Vela, J., Andersen, A. B., Bejder, J., Nybo, L., Nordsborg, N. B., Rodríguez‐Carrillo, A., Enriquez, J. A., Cogliati, S., & Casuso, R. A. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117217 · Cited by 1
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Biagioni, E. M., Krassovskaia, P. M., Tiralla, G., Fisher‐Wellman, K. H., Lin, C., Altazan, A. D., Hebert, R. C., Yendamuri, S., Singh, M., Carmichael, O. T., et al. (2026) · Journal of the Endocrine Society · doi:10.1210/jendso/bvag093 · Cited by 1
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Effects of Withania somnifera (Ashwagandha) Supplementation on Exercise Performance: A Systematic Review and Three-Level Meta-Analysis
Li, X., Li, H., Yao, S., Hou, Y., & Chi, A. (2026) · Nutrients · doi:10.3390/nu18121915 · Cited by 1
Ammonium chloride administration prevents training-induced improvements in mitochondrial respiratory function in the soleus muscle of male rats
Genders, A. J., Kuang, J., Saner, N. J., Botella, J., & Bishop, D. J. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00165.2022 · Cited by 1
Self-citation
An Exploratory Study on Whether the Interference Effect Occurs When High-Intensity Strength Training Is Performed Prior to High-Intensity Interval Aerobic Training
Bernedo, G. O., Haseler, L. J., Netto, K., & Chapman, D. W. (2024) · Applied Sciences · doi:10.3390/app14188447 · Cited by 1
Is maximal oxygen consumption an appropriate metric for metabolic health?
Lovell, D. I., Stuelcken, M., & Eagles, A. N. (2025) · European Journal of Applied Physiology · doi:10.1007/s00421-025-05875-2 · Cited by 1
“This may explain why some studies have found a significant correlation between the mitochondria and ̇ V O 2 max (Granata et al. 2018; Holloszy 1967), while others have found considerable disparity between ̇ V O 2 max and mitochondrial content (Boushel et al. 2011; Granata et al. 2016; Jacques et…”
High-Intensity Interval and Moderate-Intensity Continuous Training: Effect on Athletes' Athletic Performance
Ravalo, M. (2025) · Psychology and Education A Multidisciplinary Journal · doi:10.70838/pemj.490504 · Cited by 1
Ammonium chloride administration prior to exercise has muscle‐specific effects on mitochondrial and myofibrillar protein synthesis in rats
Genders, A. J., Marin, E. C. S., Bass, J. J., Kuang, J., Saner, N. J., Smith, K., Atherton, P. J., & Bishop, D. J. (2021) · Physiological Reports · doi:10.14814/phy2.14797 · Cited by 1
“Exercise training increases mitochondrial content and respiratory function (Granata et al., 2018), and this has been attributed to the cumulative effects of each This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and…”
BackgroundSelf-citation
Forty high-intensity interval training sessions blunt exercise-induced changes in the nuclear protein content of PGC-1α and p53 in human skeletal musclePreprint
Granata, C., Oliveira, R. S. F., Little, J. P., & Bishop, D. J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/580373 · Cited by 1
“The same absolute workload was chosen as this approach is often used in training studies 78 (22), as well as in practice, where individuals regularly repeat the same exercise session.”
BackgroundMethodSelf-citation
Rebuttal from David J. Bishop, Javier Botella and Cesare Granata
Bishop, D. J., Botella, J., & Granata, C. (2019) · The Journal of Physiology · doi:10.1113/jp278329 · Cited by 1
“For example, we have reported no significant correlation between exercise-induced changes in PGC-1α mRNA and training-induced changes in CS activity (Granata et al. 2018), and a mismatch between the effects of exercise intensity on cellular events and changes in mitochondrial content (Granata et al.”
Self-citation
Rebuttal from Martin MacInnis, Lauren Skelly and Martin Gibala
MacInnis, M. J., Skelly, L. E., & Gibala, M. J. (2019) · The Journal of Physiology · doi:10.1113/jp278328
“Firstly, on average, 37% more training sessions were performed for the moderate-intensity continuous training (MICT) as compared to high-intensity interval training (HIIT) and sprint interval training (SIT) (Granata et al. 2018): the HIIT and SIT interventions involved 15 sessions (lasting 15 min) compared to 21 sessi…”
BackgroundMethodInfluential
Farklı aerobik kapasiteye sahip kişilerde yağ oksidasyon devamlılığının takibi
Özdemir, Ç., Günaştı, Ö., Özgünen, K., Kılcı, A., Eryılmaz, S. K., & Kurdak, S. S. (2019) · Çukurova medical journal (Online)/Çukurova medical journal · doi:10.17826/cumj.578040
Sedanter bireyler ve sporcularda substrat kesişim noktasındaki yağ oksidasyon hızlarının karşılaştırılması
Günaştı, Ö., Özdemir, Ç., Özgünen, K., Kılcı, A., Eryılmaz, S. K., & Kurdak, S. S. (2019) · Çukurova medical journal (Online)/Çukurova medical journal · doi:10.17826/cumj.571942
The alteration of PGC-1α expression in younger non-professional athletes with acute medium intensity exercise model
Ariyadi, I., Susanto, H., Taufiq, A., Sugiharto, S., Merawati, D., Badu, K. M., Purnomo, J. D. T., Pertiwi, M. P., Khasna, E. N., & Ardana, I. K. K. G. (2020) · AIP conference proceedings · doi:10.1063/5.0002470
Changes in insulin resistance do not occur in parallel with changes in mitochondrial content and function in male ratsPreprint
Genders, A. J., Kuang, J., Marin, E. C. S., Saner, N. J., Botella, J., Jacques, M., McConell, G. K., Andrade‐Souza, V. A., Chagolla, J., & Bishop, D. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.06.190702
“13 As changes in mitochondrial content and function can be dissociated [17, 38], we also investigated the effects of HFD on mitochondrial respiratory function.”
BackgroundSelf-citation
Crossfit Practice: An Electromyographic Analysis of Masticatory MusclesPreprint
da Silva, N. S., Palinkas, M., Fioco, E. M., Verri, É. D., Fabrin, S., Prandi, M. V. R., Gomes, G. G. C., Regalo, I. H., Hallak, J. E. C., Regalo, S. C. H., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-117806/v1
“Physical training has the function of favoring the remodeling of the proteins that make up the skeletal striated musculature, providing molecular adaptations, and improving mitochondrial breathing [26], which results in better physical performance with increased resistance to fatigue and reduced muscle activity [27].”
Background
Effects of work-matched high-intensity intermittent cycling training with different loads and cadences on Wingate anaerobic test performance in university athletes
Tomabechi, N., Takizawa, K., Shibata, K., & Mizuno, M. (2021) · The Journal of Physical Fitness and Sports Medicine · doi:10.7600/jpfsm.10.191
Effect of 12 weeks of HIIT and Q10 supplementation on soleus muscle mitochondrial biogenesis in high-fat diet-induced obese rats
Rafati, M., Bashiri, J., Jadidi, R. P., & Pourrazi, H. (2022) · Journal of Sport and Exercise Physiology · doi:10.52547/joeppa.15.2.29

Authors: Granata, C., Jamnick, N. A., & Bishop, D. J.
Affiliations: Monash University (AU)
Victoria University (AU)
Edith Cowan University (AU)
Corresponding author: Granata, Cesare
ORCID: Granata, Cesare
Jamnick, Nicholas A.
Bishop, David J.
Venue: Sports Medicine
Publisher: Springer Science and Business Media LLC
Published: 2018-06-22
Volume: 48
Issue: 8
Pages: 1809-1828
ISSN: 0112-1642 (ISSN-L)
1179-2035
DOI: 10.1007/s40279-018-0936-y
OpenAlex: W2809197837
Cited by: 247
References: 177
Citations by year: 2026: 27 · 2025: 37 · 2024: 30 · 2023: 33 · 2022: 34 · 2021: 32 · 2020: 23 · 2019: 25 · 2018: 6
FWCI: 5.03
Type: journal article
Language: en
Open access: green
vuir.vu.edu.au
Licence: www.springer.com/tdm (tdm)
Locations: Sports Medicine (publishedVersion)
PubMed (publishedVersion)
Victoria University Research Repository (Victoria University) (submittedVersion)
Research Online (Edith Cowan University) (submittedVersion)
Deakin Research Online (Deakin University) (submittedVersion)
Figshare (submittedVersion, cc-by)
Topics: Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
Keywords: mitochondrial biogenesis, mitochondrial content, mitochondrial respiratory function, endurance training, skeletal muscle, exercise intensity, training volume, mitochondrial translation, sedentary lifestyle, training effects
MeSH terms: Adaptation, Physiological, Exercise Test, Humans, Mitochondria, Muscle, Oxygen Consumption, Exercise, Muscle, Skeletal, Cell Respiration, Physical Conditioning, Human

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Training-Induced Changes in Mitochondrial Content and Respiratory Function in Human Skeletal Muscle

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