AccScience Publishing / JCTR / Volume 10 / Issue 6 / DOI: 10.36922/jctr.24.00044
ORIGINAL ARTICLE

Effect of high-intensity interval and endurance training with MitoQ on  mitochondrial dynamics in rat muscle

Soheil Aminizadeh1 Hamid Najafipour2 Yaser Masoumi-Ardakani3 Beydolah Shahouzehi4* Mohammad Pourranjbar5
Show Less
1 Physiology Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
2 Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
3 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
4 Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
5 Department of Physical Education, Faculty of Medicine and Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran
JCTR 2024, 10(6), 348–356; https://doi.org/10.36922/jctr.24.00044
Submitted: 22 July 2024 | Revised: 9 December 2024 | Accepted: 9 December 2024 | Published: 24 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background and Aim: Mitochondria play an important role in signaling and metabolic pathways in skeletal muscle. In this study, the effects of MitoQ supplementation alone and in combination with endurance training (ET) or high-intensity interval training (HIIT) were investigated in relation to the process of mitochondrial quality control in the gastrocnemius muscle of male rats.
Methods: Animals were assigned into 6 groups (n = 7): Control, MitoQ, ET, ET + MitoQ, HIIT, and HIIT + MitoQ. The gene and protein expression were quantified using real-time polymerase chain reaction (2-ΔΔCT) and Western blot analysis, respectively. Statistical analysis was performed using one-way analysis of variance.
Results: ET significantly increased protein expression of dynamin-related protein 1 (DRP1) and mitofusin1 (MFN1) and gene expression of optic atrophy Type 1 (Opa1) in skeletal muscle, when compared to the control group (p < 0.001). HIIT only increased MFN1 protein expression compared to the control group (p < 0.0001). MitoQ in combination with HIIT significantly increased protein expression of DRP1 and MFN1 compared to MitoQ alone (p < 0.01).
Conclusion: In sum, exercise training can affect mitochondrial dynamics by changing the factors involved in the fission and fusion process, and ET can improve training capacity in skeletal muscle by modulating expression of OPA1 and MFN1. While MitoQ supplementation alone did not significantly alter the mitochondrial fission-fusion process, its combination with HIIT appeared to elevate the expression of DRP1, suggesting a potential synergistic effect that warrants further investigation. Future studies should delve into the mechanisms by which MitoQ and exerciseinduced stress affect mitochondrial quality control, particularly in the context of redox modulation and signaling pathways that govern mitochondrial plasticity.
Relevance for Patients: Combining MitoQ with exercise training may enhance mitochondrial function, potentially improving muscle health in patients.

Keywords
MitoQ
Exercise training
Fission
Fusion
Mitochondrial dynamic
Conflict of interest
The authors declare they have no competing interests.
References

[1] Karbowski M. Mitochondria on Guard: Role of Mitochondrial Fusion and Fission in the Regulation of Apoptosis. Adv Exp Med Biol 2010;687:131-42.

doi: 10.1007/978-1-4419-6706-0_8

[2] Wu T, Li Z, Wei Y. Advances in Understanding Mechanisms Underlying Mitochondrial Structure and Function Damage by Ozone. Sci Total Environ 2023;861:160589.

doi: 10.1016/j.scitotenv.2022.160589

[3] Memme JM, Erlich AT, Phukan G, Hood DA. Exercise and Mitochondrial Health. J Physiol 2021;599:803-17. doi: 10.1113/JP278853

[4] Meng Q, Su CH. The Impact of Physical Exercise on Oxidative and Nitrosative Stress: Balancing the Benefits and Risks. Antioxidants (Basel) 2024;13:573.

doi: 10.3390/antiox13050573

[5] Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab 2012;23:459-66.

doi: 10.1016/j.tem.2012.06.006

[6] Slavin MB, Khemraj P, Hood DA. Exercise, mitochondrial dysfunction and inflammasomes in skeletal muscle. Biomed J 2024;47:100636.

doi: 10.1016/j.bj.2023.100636

[7] Sokolova I. Mitochondrial Adaptations to Variable Environments and their Role in Animals’ Stress Tolerance. Integr Comp Biol 2018;58:519-31.

doi: 10.1093/icb/icy017

[8] Jenner A, Pena-Blanco A, Salvador-Gallego R, Ugarte-Uribe B, Zollo C, Ganief T, et al. Drp1 Interacts Directly with Bax to Induce its Activation and Apoptosis. EMBO J 2022;41:e108587.

doi: 10.15252/embj.2021108587

[9] Bhat S, Chin A, Shirakabe A, Ikeda Y, Ikeda S, Zhai P,et al. Recruitment of RNA Polymerase ii to Metabolic Gene Promoters is Inhibited in the Failing Heart Possibly through PGC-1Alpha (Peroxisome Proliferator-activated Receptor-Gamma Coactivator-1Alpha) Dysregulation. Circ Heart Fail 2019;12:e005529.

doi: 10.1161/CIRCHEARTFAILURE.118.005529

[10] Gureev AP, Shaforostova EA, Popov VN. Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction between the nrf2 and pgc-1alpha Signaling Pathways. Front Genet 2019;10:435.

doi: 10.3389/fgene.2019.00435

[11] Menezes TN, Ramalho LS, Bechara LR, Ferreira JCB.Targeting Mitochondrial Fission-fusion Imbalance in Heart Failure. Curr Tissue Microenviron Rep 2020;1:239-47.

[12] Youle RJ, Van der Bliek AM. Mitochondrial Fission,Fusion, and Stress. Science 2012;337:1062-5. doi: 10.1126/science.1219855

[13] Hernandez-Resendiz S, Prunier F, Girao H, Dorn G,Hausenloy DJ, Action E-CC. Targeting Mitochondrial Fusion and Fission Proteins for Cardioprotection. J Cell Mol Med 2020;24:6571-85.

[14] Schrepfer E, Scorrano L. Mitofusins, from Mitochondria to Metabolism. Mol Cell 2016;61:683-94. doi: 10.1016/j.molcel.2016.02.022

[15] Filadi R, Pendin D, Pizzo P. Mitofusin 2: From Functions to Disease. Cell Death Dis 2018;9:330. doi: 10.1038/s41419-017-0023-6

[16] Ihenacho UK, Meacham KA, Harwig MC,Widlansky ME, Hill RB. Mitochondrial Fission Protein 1: Emerging Roles in Organellar form and Function in Health and Disease. Front Endocrinol
(Lausanne) 2021;12:660095.

doi: 10.3389/fendo.2021.660095

[17] Mao P, Manczak M, Shirendeb UP, Reddy PH.MitoQ, a Mitochondria-targeted Antioxidant, Delays Disease Progression and Alleviates Pathogenesis in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis. Biochim Biophys Acta 2013;1832:2322-31.

doi: 10.1016/j.bbadis.2013.09.005

[18] Tauskela JS. MitoQ--a Mitochondria-Targeted Antioxidant. IDrugs 2007;10:399-412.

[19] Pham T, MacRae CL, Broome SC, D’Souza RF, Narang R,Wang HW, et al. MitoQ and CoQ10 Supplementation Mildly Suppresses Skeletal Muscle Mitochondrial Hydrogen Peroxide Levels without Impacting Mitochondrial Function in Middle-aged Men. Eur J Appl Physiol 2020;120:1657-9.

[20] Sulaimon LA, Afolabi LO, Adisa RA, Ayankojo AG,Afolabi MO, Adewolu AM, et al. Pharmacological Significance of MitoQ in Ameliorating Mitochondria- Related Diseases. Adv Redox Res 2022;5:100037.
doi: 10.1016/j.arres.2022.100037

[21] Tsui KH, Li CJ. Mitoquinone Shifts Energy Metabolism to Reduce ROS-induced oxeiptosis in female granulosa cells and mouse oocytes. Aging (Albany NY) 2023;15:246-60.

doi: 10.18632/aging.204475

[22] Chen S, Wang Y, Zhang H, Chen R, Lv F, Li Z, et al.The Antioxidant MitoQ Protects Against CSE-induced Endothelial Barrier Injury and Inflammation by Inhibiting ROS and Autophagy in Human Umbilical Vein Endothelial Cells. Int J Biol Sci 2019;15:1440-51. doi: 10.7150/ijbs.30193

[23] Merry TL, Ristow M. Do Antioxidant Supplements Interfere with Skeletal Muscle Adaptation to Exercise training? J Physiol 2016;594:5135-47.

doi: 10.1113/JP270654

[24] Moore TM, Zhou Z, Cohn W, Norheim F, Lin AJ,Kalajian N, et al. The impact of exercise on mitochondrial dynamics and the role of drp1 in exercise performance and training adaptations in skeletal muscle. Mol Metab 2019;21:51-67.

doi: 10.1016/j.molmet.2018.11.012

[25] Braakhuis AJ, Nagulan R, Somerville V. The Effect of MitoQ on Aging-related Biomarkers: A Systematic Review and Meta-analysis. Oxid Med Cell Longev 2018;2018:8575263.

doi: 10.1155/2018/8575263

[26] Zadeh HJ, Roholamini Z, Aminizadeh S,Deh-Ahmadi MA. Endurance Training and MitoQ Supplementation Improve Spatial Memory, VEGF Expression, and Neurogenic Factors in Hippocampal Tissue of Rats. J Clin Transl Res 2023;9:1-7.

[27] Hu J, Cai M, Shang Q, Li Z, Feng Y, Liu B, et al. Elevated Lactate by High-Intensity Interval Training Regulates the Hippocampal Bdnf Expression and the Mitochondrial Quality Control System. Front Physiol 2021;12:629914.
doi: 10.3389/fphys.2021.629914

[28] Verboven M, Cuypers A, Deluyker D, Lambrichts I,Eijnde BO, Hansen D, et al. High Intensity Training Improves Cardiac Function in Healthy Rats. Sci Rep 2019;9:5612.

doi: 10.1038/s41598-019-42023-1

[29] Batacan RB Jr., Duncan MJ, Dalbo VJ, Connolly KJ,Fenning AS. Light-intensity and High-intensity Interval Training Improve Cardiometabolic Health in Rats. Appl Physiol Nutr Metab 2016;41:945-52.

doi: 10.1139/apnm-2016-0037

[30] Pour MB, Joukar S, Hovanloo F, Najafipour H. Long-term Low-intensity Endurance Exercise Along with Blood-flow Restriction Improves Muscle Mass and Neuromuscular Junction Compartments in Old Rats. Iran J Med Sci 2017;42:569-576.

[31] Mohammadi A, Fallah H, Shahouzehi B, Najafipour H.Effect of LXR Agonist t0901317 and MIR-33inhibitor on SIRT1-AMPK and Circulating HDL-C levels. Bulg Chem Commun 2018;50:111-8.

[32] Jiang HK, Wang YH, Sun L, He X, Zhao M, Feng ZH,et al. Aerobic interval Training Attenuates Mitochondrial Dysfunction in Rats Post-myocardial Infarction: Roles of Mitochondrial Network Dynamics. Int J Mol Sci 2014;15:5304-22.

doi: 10.3390/ijms15045304

[33] Ding H, Jiang N, Liu H, Liu X, Liu D, Zhao F, et al.Response of mitochondrial Fusion and Fission Protein Gene Expression to Exercise in rat skeletal muscle.Biochim Biophys Acta 2010;1800:250-6.
doi: 10.1016/j.bbagen.2009.08.007

[34] Hood DA, Memme JM, Oliveira AN, Triolo M.Maintenance of skeletal muscle mitochondria in health, exercise, and aging. Annu Rev Physiol 2019;81:19-41. doi: 10.1146/annurev-physiol-020518-114310

[35] Broome SC, Pham T, Braakhuis AJ, Narang R,Wang HW, Hickey AJR, et al. MitoQ Supplementation Augments Acute Exercise-induced Increases in Muscle pgc1a mRNA and Improves Training-induced Increases in Peak Power Independent of Mitochondrial Content and Function in Untrained Middle-aged Men. Redox Biol 2022;53:102341.

doi: 10.1016/j.redox.2022.102341

[36] Lee YJ, Jeong SY, Karbowski M, Smith CL, Youle RJ.Roles of the Mammalian Mitochondrial Fission and Fusion Mediators FIS1, DRP1, and OPA1 in Apoptosis.

Mol Biol Cell 2004;15:5001-11. doi: 10.1091/mbc.e04-04-0294

[37] Yoo SZ, No MH, Heo JW, Park DH, Kang JH, Kim JH,et al. Effects of Acute Exercise on Mitochondrial Function, Dynamics, and Mitophagy in Rat Cardiac and Skeletal Muscles. Int Neurourol J 2019;23:S22-31.

doi: 10.5213/inj.1938038.019

[38] Axelrod CL, Fealy CE, Mulya A, Kirwan JP.Exercise Training Remodels Human Skeletal Muscle Mitochondrial Fission and Fusion Machinery Towards a Pro-Elongation Phenotype. Acta Physiol (Oxf) 2019;225:e13216.

doi: 10.1111/apha.13216

[39] Hall AR, Burke N, Dongworth RK, Hausenloy DJ.Mitochondrial fusion and Fission Proteins: Novel Therapeutic Targets for Combating Cardiovascular disease. Br J Pharmacol 2014;171:1890-906.

doi: 10.1111/bph.12516

[40] Gioscia-Ryan RA, Battson ML, Cuevas LM, Zigler MC,Sindler AL, Seals DR. Voluntary Aerobic Exercise Increases Arterial Resilience and Mitochondrial Health with Aging in Mice. Aging (Albany NY) 2016;8:2897-914.

doi: 10.18632/aging.101099

[41] Williamson J, Hughes CM, Cobley JN, Davison GW. The Mitochondria-targeted Antioxidant MitoQ, Attenuates Exercise-induced Mitochondrial DNA Damage. Redox Biol 2020;36:101673.

doi: 10.1016/j.redox.2020.101673

[42] Kang L, Liu S, Li J, Tian Y, Xue Y, Liu X. The Mitochondria-targeted Anti-Oxidant MitoQ Protects Against Intervertebral Disc Degeneration by Ameliorating Mitochondrial Dysfunction and Redox Imbalance. Cell Prolif 2020;53:e12779.

doi: 10.1111/cpr.12779

[43] Ribeiro Junior RF, Dabkowski ER, Shekar KC,Connell KAO, Hecker PA, Murphy MP. MitoQ Improves Mitochondrial Dysfunction in Heart Failure Induced by Pressure Overload. Free Radic Biol Med 2018;117:18-29. doi: 10.1016/j.freeradbiomed.2018.01.012

[44] Lowes DA, Webster NR, Murphy MP, Galley HF.Antioxidants that Protect Mitochondria Reduce Interleukin-6 and Oxidative Stress, Improve Mitochondrial Function, and Reduce Biochemical Markers of Organ Dysfunction in a Rat Model of Acute Sepsis. Br J Anaesth 2013;110:472-80.

doi: 10.1093/bja/aes577

Share
Back to top
Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing