Exercise and mitochondrial health

Memme, Jonathan M.; Erlich, Avigail T.; Phukan, Geetika; Hood, David A.

doi:10.1113/jp278853

Cited by 343Mitochondrial Function and PathologyAdipose Tissue and MetabolismExercise and Physiological Responses

Exercise and mitochondrial health

Memme, Jonathan M., Erlich, Avigail T., Phukan, Geetika, Hood, David A.·2021·The Journal of Physiology

DOI 10.1113/jp278853

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Abstract

Mitochondrial health is an important mediator of cellular function across a range of tissues, and as a result contributes to whole‐body vitality in health and disease. Our understanding of the regulation and function of these organelles is of great interest to scientists and clinicians across many disciplines within our healthcare system. Skeletal muscle is a useful model tissue for the study of mitochondrial adaptations because of its mass and contribution to whole body metabolism. The remarkable plasticity of mitochondria allows them to adjust their volume, structure and capacity under conditions such as exercise, which is useful or improving metabolic health in individuals with various diseases and/or advancing age. Mitochondria exist within muscle as a functional reticulum which is maintained by dynamic processes of biogenesis and fusion, and is balanced by opposing processes of fission and mitophagy. The sophisticated coordination of these events is incompletely understood, but is imperative for organelle function and essential for the maintenance of an interconnected organelle network that is finely tuned to the metabolic needs of the cell. Further elucidation of the mechanisms of mitochondrial turnover in muscle could offer potential therapeutic targets for the advancement of health and longevity among our ageing populations. As well, investigating exercise modalities that are both convenient and capable of inducing robust mitochondrial adaptations are useful in fostering more widespread global adherence. To this point, exercise remains the most potent behavioural therapeutic approach for the improvement of mitochondrial health, not only in muscle, but potentially also in other tissues. image

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Aerobic exercise enhances mitochondrial quality.
“It has been recently reported that aerobic exercise enhances mitochondrial quality [30].”
From Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease (2025) · cites this paper as [30]
Exercise reactivates mitophagy, reduces accumulation of ROS, improves mitochondrial health, and delays the loss of muscle mass that accompanies various pathologies, including aging sarcopenia, heart failure, and neurogenic myopathy.
“Moreover, exercise is the best non-pharmacological strategy to reactivate mitophagy, which reduces the accumulation of ROS and thus, improves mitochondrial health and delays the loss of muscle mass that accompanies various pathologies, including aging sarcopenia, heart failure and neurogenic myopathy [224, 238–240].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [224]
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 [9]

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Ibebunjo, C., Chick, J. M., Kendall, T., Eash, J. K., Li, C., Zhang, Y., Vickers, C., Wu, Z., Clarke, B. A., Shi, J., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01036-12 · Cited by 267 · see citing works
Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle
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Selective removal of mitochondria via mitophagy: distinct pathways for different mitochondrial stresses
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Adaptations of skeletal muscle mitochondria to exercise training
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Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscleThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.
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The Neuroprotective Effects of Exercise: Maintaining a Healthy Brain Throughout Aging
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Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia
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Mitochondria express enhanced quality as well as quantity in association with aerobic fitness across recreationally active individuals up to elite athletes
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Structural changes in skeletal muscle tissue with heavy-resistance exercise
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“Historically, the expansion of muscle cell size via hypertrophy has been viewed as ‘diluting’ mitochondrial content in muscle and increasing the diffusion distances (Lüthi et al. 1986).”
Background
Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans
Gouspillou, G., Sgarioto, N., Kapchinsky, S., Purves‐Smith, F., Norris, B., Pion, C. H., Barbat‐Artigas, S., Lemieux, F., Taivassalo, T., Morais, J. A., et al. (2014) · The FASEB Journal · doi:10.1096/fj.13-242750 · Cited by 217 · see citing works
Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy
Tian, W., Li, W., Chen, Y., Yan, Z., Huang, X., Zhuang, H., Zhong, W., Chen, Y., Wu, W., Lin, C., et al. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.05.020 · Cited by 199 · see citing works
Clinical detection of sarcopenic obesity by bioelectrical impedance analysis
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Tissue-specific differences in mitochondrial activity and biogenesis
Fernández‐Vizarra, E., Enrı́quez, J. A., Martos, A. P., Montoya, J., & Fernández‐Silva, P. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.09.011 · Cited by 195 · see citing works
Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network
Vincent, A. E., White, K., Davey, T., Philips, J., Ogden, R. T., Lawless, C., Warren, C., Hall, M. G., Ng, Y. S., Falkous, G., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.010 · Cited by 195 · see citing works
Mitochondria, Muscle Health, and Exercise with Advancing Age
Carter, H. N., Chen, C. C. W., & Hood, D. A. (2015) · Physiology · doi:10.1152/physiol.00039.2014 · Cited by 191 · see citing works
Self-citation
Training for Endurance and Strength
Baar, K. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000233799.62153.19 · Cited by 181 · see citing works
Mitochondrial reticulum in limb skeletal muscle
Kirkwood, S. P., Munn, E. A., & Brooks, G. A. (1986) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1986.251.3.c395 · Cited by 179 · see citing works
Exercise affects energy metabolism and neural plasticity-related proteins in the hippocampus as revealed by proteomic analysis
Ding, Q., Vaynman, S., Souda, P., Whitelegge, J. P., & Gomez‐Pinilla, F. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05026.x · Cited by 174 · see citing works
Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation
Dietrich, M. O., Andrews, Z. B., & Horváth, T. L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2744-08.2008 · Cited by 172 · see citing works
Power Grid Protection of the Muscle Mitochondrial Reticulum
Glancy, B., Hartnell, L. M., Combs, C. A., Femnou, A., Sun, J., Murphy, E., Subramaniam, S., & Balaban, R. S. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.063 · Cited by 172 · see citing works
Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse
Iqbal, S., Ostojic, O., Singh, K., Joseph, A., & Hood, D. A. (2013) · Muscle & Nerve · doi:10.1002/mus.23838 · Cited by 169 · cited 3× · see citing works
“Both SS and IMF fractions appear visibly thinner and smaller within aged muscle compared to young counterparts, and many studies have reported decreased mitochondrial content with age (Short et al. 2003, 2005; Chabi et al. 2008; Ljubicic et al. 2009; Iqbal et al. 2013).”
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Physical exercise, reactive oxygen species and neuroprotection
Radak, Z., Suzuki, K., Higuchi, M., Balogh, L., Boldogh, I., & Koltai, E. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.01.024 · Cited by 167 · see citing works
Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle
O'Leary, M. F., Vainshtein, A., Iqbal, S., Ostojic, O., & Hood, D. A. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00240.2012 · Cited by 165 · see citing works
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Gene shifting: a novel therapy for mitochondrial myopathy
Taivassalo, T. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.6.1047 · Cited by 160 · see citing works
Selected Contribution: Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle
Gordon, J. W., Rungi, A. A., Inagaki, H., & Hood, D. A. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.1.389 · Cited by 160 · see citing works
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Unravelling the mechanisms regulating muscle mitochondrial biogenesis
Hood, D. A., Tryon, L. D., Carter, H. N., Kim, Y., & Chen, C. C. W. (2016) · Biochemical Journal · doi:10.1042/bcj20160009 · Cited by 159 · cited 1× · see citing works
“Previous reviews have provided a more complete analysis of this issue (Hood et al. 2016).”
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Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers
Marques‐Aleixo, I., Alves, E. S., Balça, M. M., Rizo‐Roca, D., Moreira, P. I., Oliveira, P. J., Magalhães, J., & Ascensão, A. A. M. R. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.06.027 · Cited by 159 · see citing works
Impact of Resistance Training on Skeletal Muscle Mitochondrial Biogenesis, Content, and Function
Groennebaek, T., & Vissing, K. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00713 · Cited by 154 · see citing works
Age-Associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training
Koltai, E., Hart, N., Taylor, A. W., Goto, S., Ngo, J. K., Davies, K. J. A., & Radak, Z. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00337.2011 · Cited by 152 · see citing works
Mediators of Physical Activity Protection against ROS-Linked Skeletal Muscle Damage
Meo, S. D., Napolitano, G., & Venditti, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20123024 · Cited by 146 · see citing works
Acute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle
Picard, M. A., Gentil, B. J., McManus, M. J., White, K., Louis, K. S., Gartside, S. E., Wallace, D. C., & Turnbull, D. M. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00819.2013 · Cited by 145 · see citing works
Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity
Carter, H. N., Kim, Y., Erlich, A. T., Zarrin‐khat, D., & Hood, D. A. (2018) · The Journal of Physiology · doi:10.1113/jp275998 · Cited by 136 · see citing works
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Mitochondrial Nanotunnels
Vincent, A. E., Turnbull, D. M., Eisner, V., Hajnóczky, G., & Picard, M. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.08.009 · Cited by 135 · see citing works
The regulation of autophagy during exercise in skeletal muscle
Vainshtein, A., & Hood, D. A. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00550.2015 · Cited by 132 · see citing works
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Autophagy plays a role in skeletal muscle mitochondrial biogenesis in an endurance exercise-trained condition
Ju, J.-S., Jeon, S.-I., Park, J.-Y., Lee, J.-Y., Lee, S.-C., Cho, K.-J., & Jeong, J.-M. (2016) · The Journal of Physiological Sciences · doi:10.1007/s12576-016-0440-9 · Cited by 125 · see citing works
Role of Parkin and endurance training on mitochondrial turnover in skeletal muscle
Chen, C. C. W., Erlich, A. T., & Hood, D. A. (2018) · Skeletal Muscle · doi:10.1186/s13395-018-0157-y · Cited by 124 · see citing works
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Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle
Marcinek, D. J., Schenkman, K. A., Ciesielski, W. A., Lee, D., & Conley, K. E. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.097782 · Cited by 123 · see citing works
Parkin overexpression protects from ageing‐related loss of muscle mass and strength
Leduc‐Gaudet, J., Reynaud, O., Hussain, S. N., & Gouspillou, G. (2019) · The Journal of Physiology · doi:10.1113/jp277157 · Cited by 119 · see citing works
Extracellular Vesicles: Delivery Vehicles of Myokines
Trovato, E., Felice, V. D., & Barone, R. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00522 · Cited by 111 · see citing works
Exercise induces TFEB expression and activity in skeletal muscle in a PGC-1α-dependent manner
Erlich, A. T., Brownlee, D., Beyfuss, K. A., & Hood, D. A. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00162.2017 · Cited by 110 · see citing works
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Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice
Gusdon, A. M., Callio, J., Distéfano, G., O'Doherty, R. M., Goodpaster, B. H., Coen, P. M., & Chu, C. T. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.01.013 · Cited by 109 · see citing works
Parkin is required for exercise-induced mitophagy in muscle: Impact of aging
Chen, C. C. W., Erlich, A. T., Crilly, M. J., & Hood, D. A. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00391.2017 · Cited by 108 · see citing works
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Physical Exercise and Brain Mitochondrial Fitness: The Possible Role Against <scp>A</scp>lzheimer's Disease
Bernardo, T. C., Marques‐Aleixo, I., Beleza, J., Oliveira, P. J., Ascensão, A., & Magalhães, J. (2016) · Brain Pathology · doi:10.1111/bpa.12403 · Cited by 108 · see citing works
Mitochondrial dysfunction and age
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Mechanisms of Exercise‐Induced Mitochondrial Biogenesis in Skeletal Muscle: Implications for Health and Disease
Hood, D. A., Uguccioni, G., Vainshtein, A., & D’Souza, D. M. (2011) · Comprehensive physiology · doi:10.1002/cphy.c100074 · Cited by 101 · see citing works
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Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle
Ljubicic, V., Joseph, A.-M., Adhihetty, P. J., Huang, J. H., Saleem, A., Uguccioni, G., & Hood, D. A. (2009) · Aging · doi:10.18632/aging.100083 · Cited by 98 · see citing works
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Emerging roles and regulation of MiT/TFE transcriptional factors
Yang, M., Liu, E., Tang, L., Lei, Y., Sun, X., Hu, J., Dong, H., Yang, S., Gao, M., & Tang, B. (2018) · Cell Communication and Signaling · doi:10.1186/s12964-018-0242-1 · Cited by 90 · see citing works
Diminished contraction‐induced intracellular signaling towards mitochondrial biogenesis in aged skeletal muscle
Ljubicic, V., & Hood, D. A. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00483.x · Cited by 87 · see citing works
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Swimming exercise increases serum irisin level and reduces body fat mass in high-fat-diet fed Wistar rats
Lu, Y., Li, H., Shen, S., Shen, Z., Xu, M., Yang, C., Li, F., Feng, Y.-B., Yun, J., Wang, L., et al. (2016) · Lipids in Health and Disease · doi:10.1186/s12944-016-0263-y · Cited by 81 · see citing works
Exercise-Induced Mitophagy in Skeletal Muscle and Heart
Guan, Y., Drake, J. C., & Yan, Z. (2019) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000192 · Cited by 79 · see citing works
Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases
Diamanti, A., Colistro, F., Basso, M. S., Papadatou, B., Francalanci, P., Bracci, F., Muraca, M., Knafelz, D., Angelis, P. D., & Castro, M. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20472 · Cited by 74 · see citing works
Mitochondrial size and shape in equine skeletal muscle: A three‐dimensional reconstruction study
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The mitochondrial unfolded protein response in mammalian physiology
Mottis, A., Jovaisaite, V., & Auwerx, J. H. (2014) · Mammalian Genome · doi:10.1007/s00335-014-9525-z · Cited by 68 · see citing works
Accumulation of severely atrophic myofibers marks the acceleration of sarcopenia in slow and fast twitch muscles
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Transcription could be the key to the selection advantage of mitochondrial deletion mutants in aging
Kowald, A., & Kirkwood, T. B. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314970111 · Cited by 58 · see citing works
Microarray Analysis Reveals Novel Features of the Muscle Aging Process in Men and Women
Liu, D., Sartor, M. A., Nader, G. A., Pistilli, E. E., Tanton, L. C., Lilly, C., Gutmann, L., IglayReger, H. B., Visich, P. S., Hoffman, E. P., et al. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt015 · Cited by 58 · see citing works
Chronology of UPR activation in skeletal muscle adaptations to chronic contractile activity
Memme, J. M., Oliveira, A. N., & Hood, D. A. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00009.2016 · Cited by 55 · see citing works
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Obesity Downregulates MicroRNA‐126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training
Gomes, J. L. P., Fernandes, T. M., Soci, Ú. P. R., Silveira, A. C., Barretti, D. L. M., Negrão, C. E., & de Oliveira, E. M. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/2415246 · Cited by 55 · see citing works
Expression and modification proteomics during skeletal muscle ageing
Baraibar, M. A., Gueugneau, M., Duguez, S., Butler-Browne, G. S., Béchet, D., & Friguet, B. (2013) · Biogerontology · doi:10.1007/s10522-013-9426-7 · Cited by 49 · see citing works
Regulation of the autophagy system during chronic contractile activity-induced muscle adaptations
Kim, Y., & Hood, D. A. (2017) · Physiological Reports · doi:10.14814/phy2.13307 · Cited by 40 · see citing works
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Mitochondrial breakdown in skeletal muscle and the emerging role of the lysosomes
Triolo, M., & Hood, D. A. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.11.004 · Cited by 39 · see citing works
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Myokine Expression in Muscle and Myotubes in Response to Exercise Stimulation
Covington, J. D., Tam, C. S., Bajpeyi, S., Galgani, J. E., Noland, R. C., Smith, S. R., Redman, L. M., & Ravussin, É. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000787 · Cited by 38 · see citing works
Resistance training increases fibroblast growth factor-21 and irisin levels in the skeletal muscle of Zucker diabetic fatty rats
Kim, H.-J., & Song, W. J. (2017) · Physical Activity and Nutrition · doi:10.20463/jenb.2017.0008 · Cited by 37 · see citing works
Nutrition and Training Influences on the Regulation of Mitochondrial Adenosine Diphosphate Sensitivity and Bioenergetics
Holloway, G. P. (2017) · Sports Medicine · doi:10.1007/s40279-017-0693-3 · Cited by 36 · see citing works
Effect of contractile activity on PGC-1α transcription in young and aged skeletal muscle.
Carter, H. N., Pauly, M., Tryon, L. D., & Hood, D. (2018) · Journal of applied physiology · doi:10.1152/japplphysiol.01110.2017 · Cited by 36 · see citing works
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Regulation of autophagic and mitophagic flux during chronic contractile activity-induced muscle adaptations
Kim, Y., Triolo, M., Erlich, A. T., & Hood, D. A. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2225-x · Cited by 36 · see citing works
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The unfolded protein response in relation to mitochondrial biogenesis in skeletal muscle cells
Moosavi, Z. S. M., & Hood, D. A. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00320.2016 · Cited by 33 · see citing works
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Effect of Tim23 knockdown in vivo on mitochondrial protein import and retrograde signaling to the UPRmt in muscle
Oliveira, A. N., & Hood, D. A. (2018) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00275.2017 · Cited by 27 · see citing works
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Resistance Exercise Improves Mitochondrial Quality Control in a Rat Model of Sporadic Inclusion Body Myositis
Koo, J., Kang, E., & Cho, J. (2019) · Gerontology · doi:10.1159/000494723 · Cited by 24 · see citing works
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Ogata (1997) · doi:10.1002/(sici)1097-0185(199706)248:2

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Exercise and the Regulation of Mitochondrial Turnover
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Authors: Memme, J. M., Erlich, A. T., Phukan, G., & Hood, D. A.
Affiliations: York University (CA)
Corresponding author: Hood, David A.
ORCID: Memme, Jonathan M.
Hood, David A.
Venue: The Journal of Physiology
Publisher: Wiley
Published: 2019-12-09
Volume: 599
Issue: 3
Pages: 803-817
ISSN: 0022-3751 (ISSN-L)
1469-7793
DOI: 10.1113/jp278853
OpenAlex: W2985749257
Cited by: 343
References: 148
Citations by year: 2026: 61 · 2025: 82 · 2024: 65 · 2023: 52 · 2022: 46 · 2021: 26 · 2020: 8 · 2016: 1 · 2015: 1 · 2013: 1
FWCI: 1.76
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Physiology (publishedVersion)
PubMed (publishedVersion)
Funders: Natural Sciences and Engineering Research Council of Canada (38462)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords: physical activity, mitochondrial health, skeletal muscle, mitochondrial biogenesis, mitochondrial fusion, mitochondrial fission, mitophagy, mitochondrial turnover, exercise adherence, aging, metabolic health, exercise modalities
MeSH terms: Organelle Biogenesis, Humans, Mitochondria, Mitochondria, Muscle, Exercise, Muscle, Skeletal, Mitophagy

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