Abstract
It is well established that physical exercise imposes increased levels of mechanical and metabolic stress to the human organism, altering the homeostasis and stimulating the inherent ability of tissues to structurally and functionally adapt to cope with the inflicted challenges. These adaptations usually result in an increased resistance against the harmful effects characterizing senescence as well as those associated with disease conditions. These include muscle myopathies, cardiac dysfunction induced by ischaemia-reperfusion, obesity, diabetes or toxicants exposure, liver and neurodegenerative diseases. In fact, exercise may directly alter cellular energy status or increase mechanical load in contractile tissues, such as skeletal and cardiac muscles, and may also indirectly induce an endocrine-like effect through the release of distinct molecules by striated muscles, which may exert consequent stimulation in non-contractile tissues, such as brain, liver or adipocytes. Mitochondrial remodelling is among the most important mechanisms targeted by exercise that contribute to the mentioned protective phenotype. The powerful influence of exercise in mitochondrial physiology include favourable changes in bioenergetics and substrate utilization, alterations in redox homeostasis, changes in network dynamics through biogenesis, fusion and fission mechanisms, an important involvement in the control of cellular death mechanisms as well as influence in cell signalling, autophagy-related renewal and quality control processes. The present review analyses the effects of exercise in the modulation of mitochondrial physiology, examining distinct proposed mechanisms targeting mitochondria and potentially responsible tissue boosting and consequent defect rescuing. The emerging role of epigenetic-based contribution to these cross-tolerance effects is also addressed.
Jorge Beleza and David Rizo-Roca contributed equally to this work.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adhihetty PJ, Ljubicic V, Hood DA (2006) Effect of chronic contractile activity on SS and IMF mitochondrial apoptotic susceptibility in skeletal muscle. AJP Endocrinol Metab 292:E748–E755. https://doi.org/10.1152/ajpendo.00311.2006
Adhihetty PJ, O’Leary MFN, Chabi B et al (2007) Effect of denervation on mitochondrially mediated apoptosis in skeletal muscle. J Appl Physiol 102:1143–1151. https://doi.org/10.1152/japplphysiol.00768.2006
Adhihetty PJ, Uguccioni G, Leick L et al (2009) The role of PGC-1alpha on mitochondrial function and apoptotic susceptibility in muscle. Am J Physiol Cell Physiol 297:C217–C225. https://doi.org/10.1152/ajpcell.00070.2009
Alleman RJ, Tsang AM, Ryan TE et al (2016) Exercise-induced protection against reperfusion arrhythmia involves stabilization of mitochondrial energetics. Am J Physiol Heart Circ Physiol 310:H1360–H1370. https://doi.org/10.1152/ajpheart.00858.2015
Alves RMP, Vitorino R, Figueiredo P et al (2010) Lifelong physical activity modulation of the skeletal muscle mitochondrial proteome in mice. J Gerontol Ser A Biol Sci Med Sci 65A:832–842. https://doi.org/10.1093/gerona/glq081
Aoi W, Naito Y, Mizushima K et al (2010) The microRNA miR-696 regulates PGC-1 in mouse skeletal muscle in response to physical activity. AJP Endocrinol Metab 298:E799–E806. https://doi.org/10.1152/ajpendo.00448.2009
Ascensão A, Magalhães J, Soares J et al (2005a) Endurance training attenuates doxorubicin-induced cardiac oxidative damage in mice. Int J Cardiol 100:451–460. https://doi.org/10.1016/j.ijcard.2004.11.004
Ascensão A, Magalhães J, Soares JMC et al (2005b) Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. Am J Phys 289:H722–H731. https://doi.org/10.1152/ajpheart.01249.2004
Ascensão A, Ferreira R, Oliveira PJ, Magalhães J (2006a) Effects of endurance training and acute doxorubicin treatment on rat heart mitochondrial alterations induced by in vitro anoxia-reoxygenation. Cardiovasc Toxicol 6:159–172
Ascensão A, Magalhães J, Soares JMC et al (2006b) Endurance training limits the functional alterations of heart rat mitochondria submitted to in vitro anoxia-reoxygenation. Int J Cardiol 109:169–178. https://doi.org/10.1016/j.ijcard.2005.06.003
Ascensão A, Ferreira R, Magalhães J (2007) Exercise-induced cardioprotection—biochemical, morphological and functional evidence in whole tissue and isolated mitochondria. Int J Cardiol 117:16–30. https://doi.org/10.1016/j.ijcard.2006.04.076
Ascensão A, Lumini-Oliveira J, Oliveira P, Magalhaes J (2011a) Mitochondria as a target for exercise-induced cardioprotection. Curr Drug Targets 12:860–871. https://doi.org/10.2174/138945011795529001
Ascensão A, Lumini-Oliveira J, Machado NG et al (2011b) Acute exercise protects against calcium-induced cardiac mitochondrial permeability transition pore opening in doxorubicin-treated rats. Clin Sci (Lond) 120:37–49. https://doi.org/10.1042/CS20100254
Ascensão A, Gonçalves IO, Lumini-Oliveira J et al (2012a) Endurance training and chronic intermittent hypoxia modulate in vitro salicylate-induced hepatic mitochondrial dysfunction. Mitochondrion 12:607–616. https://doi.org/10.1016/j.mito.2012.10.007
Ascensão A, Oliveira PJ, Magalhães J (2012b) Exercise as a beneficial adjunct therapy during doxorubicin treatment-role of mitochondria in cardioprotection. Int J Cardiol 156:4–10. https://doi.org/10.1016/j.ijcard.2011.05.060
Ascensão A, Martins MJ, Santos-Alves E et al (2013) Modulation of hepatic redox status and mitochondrial metabolism by exercise: therapeutic strategy for liver diseases. Mitochondrion 13:862–870. https://doi.org/10.1016/j.mito.2013.07.002
Ballmann C, McGinnis G, Peters B et al (2014) Exercise-induced oxidative stress and hypoxic exercise recovery. Eur J Appl Physiol 114:725–733. https://doi.org/10.1007/s00421-013-2806-5
Barrès R, Yan J, Egan B et al (2012) Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 15:405–411. https://doi.org/10.1016/j.cmet.2012.01.001
Bayod S, del Valle J, Lalanza JF et al (2012) Long-term physical exercise induces changes in sirtuin 1 pathway and oxidative parameters in adult rat tissues. Exp Gerontol 47:925–935. https://doi.org/10.1016/j.exger.2012.08.004
Befroy DE, Petersen KF, Dufour S et al (2008) Increased substrate oxidation and mitochondrial uncoupling in skeletal muscle of endurance-trained individuals. Proc Natl Acad Sci U S A 105:16701–16706. https://doi.org/10.1073/pnas.0808889105
Bernardo TC, Marques-Aleixo I, Beleza J et al (2016) Physical exercise and brain mitochondrial fitness: the possible role against Alzheimer’s disease. Brain Pathol 26:648–663. https://doi.org/10.1111/bpa.12403
Bo H, Kang W, Jiang N et al (2014) Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase. Oxidative Med Cell Longev 2014:834502. https://doi.org/10.1155/2014/834502
Booth FW, Ruegsegger GN, Toedebusch RG, Yan Z (2015) Endurance exercise and the regulation of skeletal muscle metabolism. Prog Mol Biol Transl Sci 135:129–151
Boström P, Wu J, Jedrychowski MP et al (2012) A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468. https://doi.org/10.1038/nature10777
Boveris A, Navarro A (2008) Systemic and mitochondrial adaptive responses to moderate exercise in rodents. Free Radic Biol Med 44:224–229. https://doi.org/10.1016/j.freeradbiomed.2007.08.015
Brown DA, Chicco AJ, Jew KN et al (2005) Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the K ATP channel in the rat. J Physiol 569:913–924. https://doi.org/10.1113/jphysiol.2005.095729
Brown DA, Perry JB, Allen ME et al (2016) Expert consensus document: mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol 14:238–250. https://doi.org/10.1038/nrcardio.2016.203
Burgomaster KA, Howarth KR, Phillips SM et al (2008) Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J Physiol 586:151–160. https://doi.org/10.1113/jphysiol.2007.142109
Campos JC, Queliconi BB, Dourado PMM et al (2012) Exercise training restores cardiac protein quality control in heart failure. PLoS One 7:e52764. https://doi.org/10.1371/journal.pone.0052764
Cantó C, Gerhart-Hines Z, Feige JN et al (2009) AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458:1056–1060. https://doi.org/10.1038/nature07813
Cao W, Daniel KW, Robidoux J et al (2004) p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol 24:3057–3067. https://doi.org/10.1128/mcb.24.7.3057-3067.2004
Carter HN, Chen CCW, Hood DA (2015) Mitochondria, muscle health, and exercise with advancing age. Physiology 30:208–223. https://doi.org/10.1152/physiol.00039.2014
Cartoni R, Léger B, Hock MB et al (2005) Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. J Physiol 567:349–358. https://doi.org/10.1113/jphysiol.2005.092031
Cheng A, Yang Y, Zhou Y et al (2016) Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges. Cell Metab 23:128–142. https://doi.org/10.1016/j.cmet.2015.10.013
Chicco AJ, Schneider CM, Hayward R (2005) Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart. Am J Physiol Regul Integr Comp Physiol 289:R424–R431. https://doi.org/10.1152/ajpregu.00636.2004
Chicco AJ, Hydock DS, Schneider CM, Hayward R (2006) Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity. J Appl Physiol 100:519–527. https://doi.org/10.1152/japplphysiol.00148.2005
Chung E, Joiner HE, Skelton T et al (2017) Maternal exercise upregulates mitochondrial gene expression and increases enzyme activity of fetal mouse hearts. Physiol Rep 5:e13184. https://doi.org/10.14814/phy2.13184
Ciminelli M, Ascah A, Bourduas K, Burelle Y (2006) Short term training attenuates opening of the mitochondrial permeability transition pore without affecting myocardial function following ischemia-reperfusion. Mol Cell Biochem 291:39–47. https://doi.org/10.1007/s11010-006-9192-9
Cribbs JT, Strack S (2007) Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 8:939–944. https://doi.org/10.1038/sj.embor.7401062
Dembele K, Nguyen KH, Hernandez TA, Nyomba BLG (2009) Effects of ethanol on pancreatic beta-cell death: interaction with glucose and fatty acids. Cell Biol Toxicol 25:141–152. https://doi.org/10.1007/s10565-008-9067-9
Denham J, Marques FZ, O’Brien BJ, Charchar FJ (2014) Exercise: putting action into our epigenome. Sport Med 44:189–209. https://doi.org/10.1007/s40279-013-0114-1
Dietrich MO, Andrews ZB, Horvath TL (2008) Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaptation. J Neurosci 28:10766–10771. https://doi.org/10.1523/JNEUROSCI.2744-08.2008
Dolinsky VW, Rogan KJ, Sung MM et al (2013) Both aerobic exercise and resveratrol supplementation attenuate doxorubicin-induced cardiac injury in mice. AJP Endocrinol Metab 305:E243–E253. https://doi.org/10.1152/ajpendo.00044.2013
Donovan EL, Miller BF (2011) Exercise during pregnancy: developmental origins of disease prevention? Exerc Sport Sci Rev 39:111. https://doi.org/10.1097/JES.0b013e31821f7d78
Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95. https://doi.org/10.1152/physrev.00018.2001
Dudley GA, Abraham WM, Terjung RL (1982) Influence of exercise intensity and duration on biochemical adaptations in skeletal muscle. J Appl Physiol 53:844–850
Egan B, Zierath JR (2013) Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 17:162–184. https://doi.org/10.1016/j.cmet.2012.12.012
Egan D, Kim J, Shaw RJ, Guan K-L (2011) The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy 7:643–644
Figueiredo PA, Powers SK, Ferreira RM et al (2009) Impact of lifelong sedentary behavior on mitochondrial function of mice skeletal muscle. J Gerontol Ser A Biol Sci Med Sci 64A:927–939. https://doi.org/10.1093/gerona/glp066
Fiuza-Luces C, Garatachea N, Berger NA, Lucia A (2013) Exercise is the real polypill. Physiology 28:330–358. https://doi.org/10.1152/physiol.00019.2013
Frank S, Gaume B, Bergmann-Leitner ES et al (2001) The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 1:515–525
Fromenty B, Robin MA, Igoudjil A et al (2004) The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab 30:121–138
Garnier A, Fortin D, Zoll J et al (2005) Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle. FASEB J 19:43–52. https://doi.org/10.1096/fj.04-2173com
Gibala MJ, MacLean DA, Graham TE, Saltin B (1998) Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am J Phys 275:E235–E242
Gomez-Cabrera M-C, Domenech E, Romagnoli M et al (2008) Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 87:142–149
Gonçalves IO, Oliveira PJ, Ascensão A, Magalhães J (2013) Exercise as a therapeutic tool to prevent mitochondrial degeneration in nonalcoholic steatohepatitis. Eur J Clin Invest 43(11):1184–1194. https://doi.org/10.1111/eci.12146
Gonçalves IO, Maciel E, Passos E et al (2014a) Exercise alters liver mitochondria phospholipidomic profile and mitochondrial activity in non-alcoholic steatohepatitis. Int J Biochem Cell Biol 54:163–173. https://doi.org/10.1016/j.biocel.2014.07.011
Gonçalves IO, Passos E, Rocha-Rodrigues S et al (2014b) Physical exercise prevents and mitigates non-alcoholic steatohepatitis-induced liver mitochondrial structural and bioenergetics impairments. Mitochondrion 15:40–51. https://doi.org/10.1016/j.mito.2014.03.012
Gonçalves IO, Passos E, Diogo CV et al (2016) Exercise mitigates mitochondrial permeability transition pore and quality control mechanisms alterations in nonalcoholic steatohepatitis. Appl Physiol Nutr Metab 41:298–306. https://doi.org/10.1139/apnm-2015-0470
Gounder SS, Kannan S, Devadoss D et al (2012) Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training. PLoS One 7:e45697. https://doi.org/10.1371/journal.pone.0045697
Gusdon AM, Callio J, Distefano G et al (2017) Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice. Exp Gerontol 90:1–13. https://doi.org/10.1016/j.exger.2017.01.013
Haase TN, Ringholm S, Leick L et al (2011) Role of PGC-1 in exercise and fasting-induced adaptations in mouse liver. AJP Regul Integr Comp Physiol 301:R1501–R1509. https://doi.org/10.1152/ajpregu.00775.2010
Henriksson J (1977) Training induced adaptation of skeletal muscle and metabolism during submaximal exercise. J Physiol 270:661–675
Herbst EAF, Roussakis C, Matravadia S, Holloway GP (2015) Chronic treadmill running does not enhance mitochondrial oxidative capacity in the cortex or striatum. Metabolism 64:1419–1425. https://doi.org/10.1016/j.metabol.2015.07.002
Hickson RC (1981) Skeletal muscle cytochrome c and myoglobin, endurance, and frequency of training. J Appl Physiol 51:746–749
Hoffmann C, Weigert C (2017) Skeletal muscle as an endocrine organ: the role of myokines in exercise adaptations. Cold Spring Harb Perspect Med 7(11):a029793. https://doi.org/10.1101/cshperspect.a029793
Holloszy JO (1967) Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem 242:2278–2282
Holloszy JO, Coyle EF (1984) Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56:831–838
Hood DA, Tryon LD, Carter HN et al (2016) Unravelling the mechanisms regulating muscle mitochondrial biogenesis. Biochem J 473:2295–2314. https://doi.org/10.1042/BCJ20160009
Hoppeler H, Howald H, Conley K et al (1985) Endurance training in humans: aerobic capacity and structure of skeletal muscle. J Appl Physiol 59:320–327
Horowitz JF, Leone TC, Feng W et al (2000) Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. Am J Physiol Endocrinol Metab 279:E348–E355
Iizuka K, Machida T, Hirafuji M (2014) Skeletal muscle is an endocrine organ. J Pharmacol Sci 125:125–131
Ingjer F (1979) Capillary supply and mitochondrial content of different skeletal muscle fiber types in untrained and endurance-trained men. A histochemical and ultrastructural study. Eur J Appl Physiol Occup Physiol 40:197–209
Jacobs RA, Lundby C (2013) Mitochondria express enhanced quality as well as quantity in association with aerobic fitness across recreationally active individuals up to elite athletes. J Appl Physiol 114:344–350. https://doi.org/10.1152/japplphysiol.01081.2012
Jäger S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A 104:12017–12022. https://doi.org/10.1073/pnas.0705070104
Jansson E, Kaijser L (1987) Substrate utilization and enzymes in skeletal muscle of extremely endurance-trained men. J Appl Physiol 62:999–1005
Jendrach M, Mai S, Pohl S et al (2008) Short- and long-term alterations of mitochondrial morphology, dynamics and mtDNA after transient oxidative stress. Mitochondrion 8:293–304. https://doi.org/10.1016/j.mito.2008.06.001
Ji LL, Kang C, Zhang Y (2016) Exercise-induced hormesis and skeletal muscle health. Free Radic Biol Med 98:113–122. https://doi.org/10.1016/j.freeradbiomed.2016.02.025
Jiménez-Chillarón JC, Nijland MJ, Ascensão AA et al (2015) Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling. Epigenetics 10:259–273. https://doi.org/10.1080/15592294.2015.1020267
Joseph A-M, Adhihetty PJ, Leeuwenburgh C (2016) Beneficial effects of exercise on age-related mitochondrial dysfunction and oxidative stress in skeletal muscle. J Physiol 594:5105–5123. https://doi.org/10.1113/JP270659
Kang C, O’Moore KM, Dickman JR, Ji LL (2009) Exercise activation of muscle peroxisome proliferator-activated receptor-γ coactivator-1α signaling is redox sensitive. Free Radic Biol Med 47:1394–1400. https://doi.org/10.1016/j.freeradbiomed.2009.08.007
Kang C, Chung E, Diffee G, Ji LL (2013) Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α. Exp Gerontol 48:1343–1350. https://doi.org/10.1016/j.exger.2013.08.004
Kapilevich LV, Kironenko TA, Zaharova AN et al (2015) Skeletal muscle as an endocrine organ: role of [Na+]i/[K+]i-mediated excitation-transcription coupling. Genes Dis 2:328–336. https://doi.org/10.1016/j.gendis.2015.10.001
Kavazis AN, McClung JM, Hood DA, Powers SK (2008) Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli. Am J Physiol Heart Circ Physiol 294:H928–H935. https://doi.org/10.1152/ajpheart.01231.2007
Kavazis AN, Alvarez S, Talbert E et al (2009) Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins. AJP Heart Circ Physiol 297:H144–H152. https://doi.org/10.1152/ajpheart.01278.2008
Kavazis AN, Smuder AJ, Min K et al (2010) Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol 299:H1515–H1524. https://doi.org/10.1152/ajpheart.00585.2010
Kavazis AN, Smuder AJ, Powers SK (2014) Effects of short-term endurance exercise training on acute doxorubicin-induced FoxO transcription in cardiac and skeletal muscle. J Appl Physiol 117:223–230. https://doi.org/10.1152/japplphysiol.00210.2014
Kirby TJ, McCarthy JJ (2013) MicroRNAs in skeletal muscle biology and exercise adaptation. Free Radic Biol Med 64:95–105. https://doi.org/10.1016/j.freeradbiomed.2013.07.004
Klotz L-O, Sánchez-Ramos C, Prieto-Arroyo I et al (2015) Redox regulation of FoxO transcription factors. Redox Biol 6:51–72. https://doi.org/10.1016/j.redox.2015.06.019
Koltai E, Hart N, Taylor AW et al (2012) Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training. AJP Regul Integr Comp Physiol 303:R127–R134. https://doi.org/10.1152/ajpregu.00337.2011
Konopka AR, Suer MK, Wolff CA, Harber MP (2014) Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training. J Gerontol Ser A Biol Sci Med Sci 69:371–378. https://doi.org/10.1093/gerona/glt107
Laker RC, Lillard TS, Okutsu M et al (2014) Exercise prevents maternal high-fat diet-induced hypermethylation of the Pgc-1α gene and age-dependent metabolic dysfunction in the offspring. Diabetes 63:1605–1611. https://doi.org/10.2337/db13-1614
Larsen S, Nielsen J, Hansen CN et al (2012) Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol 590:3349–3360. https://doi.org/10.1113/jphysiol.2012.230185
Larsen S, Danielsen JH, Søndergård SD et al (2015) The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue. Scand J Med Sci Sports 25:e59–e69. https://doi.org/10.1111/sms.12252
Leboucher GP, Tsai YC, Yang M et al (2012) Stress-induced phosphorylation and proteasomal degradation of mitofusin 2 facilitates mitochondrial fragmentation and apoptosis. Mol Cell 47:547–557. https://doi.org/10.1016/j.molcel.2012.05.041
Lee Y, Min K, Talbert EE et al (2012) Exercise protects cardiac mitochondria against ischemia-reperfusion injury. Med Sci Sports Exerc 44:397–405. https://doi.org/10.1249/MSS.0b013e318231c037
Leichtweis SB, Leeuwenburgh C, Parmelee DJ et al (1997) Rigorous swim training impairs mitochondrial function in post-ischaemic rat heart. Acta Physiol Scand 160:139–148. https://doi.org/10.1046/j.1365-201X.1997.00138.x
Leick L, Lyngby SS, Wojtasewski JF et al (2010) PGC-1α is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle. Exp Gerontol 45:336–342. https://doi.org/10.1016/j.exger.2010.01.011
Lin J, Wu H, Tarr PT et al (2002) Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. Nature 418:797–801. https://doi.org/10.1038/nature00904
Lira VA, Okutsu M, Zhang M et al (2013) Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. FASEB J 27:4184–4193. https://doi.org/10.1096/fj.13-228486
Little JP, Safdar A, Benton CR, Wright DC (2011) Skeletal muscle and beyond: the role of exercise as a mediator of systemic mitochondrial biogenesis. Appl Physiol Nutr Metab 36:598–607. https://doi.org/10.1139/h11-076
van Loon LJ, Greenhaff PL, Constantin-Teodosiu D et al (2001) The effects of increasing exercise intensity on muscle fuel utilisation in humans. J Physiol 536:295–304. https://doi.org/10.1111/j.1469-7793.2001.00295.x
Lumini JA, Magalhães J, Oliveira PJ, Ascensão A (2008) Beneficial effects of exercise on muscle mitochondrial function in diabetes mellitus. Sports Med 38:735–750
Lumini-Oliveira J, Magalhães J, Pereira CV et al (2011) Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia. Mitochondrion 11:54–63. https://doi.org/10.1016/j.mito.2010.07.005
Lundby C, Jacobs RA (2016) Adaptations of skeletal muscle mitochondria to exercise training. Exp Physiol 101:17–22. https://doi.org/10.1113/EP085319
MacInnis MJ, Zacharewicz E, Martin BJ et al (2016) Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol. https://doi.org/10.1113/JP272570
Magalhães J, Falcão-Pires I, Gonçalves IO et al (2013) Synergistic impact of endurance training and intermittent hypobaric hypoxia on cardiac function and mitochondrial energetic and signaling. Int J Cardiol 168:5363–5371. https://doi.org/10.1016/j.ijcard.2013.08.001
Magalhães J, Gonçalves IO, Lumini-Oliveira J et al (2014) Modulation of cardiac mitochondrial permeability transition and apoptotic signaling by endurance training and intermittent hypobaric hypoxia. Int J Cardiol 173:40–45. https://doi.org/10.1016/j.ijcard.2014.02.011
Marcelino TB, Longoni A, Kudo KY et al (2013) Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats. Neuroscience 246:28–39. https://doi.org/10.1016/j.neuroscience.2013.04.043
Marcil M, Bourduas K, Ascah A, Burelle Y (2005) Exercise training induces respiratory substrate-specific decrease in Ca2+-induced permeability transition pore opening in heart mitochondria. AJP Heart Circ Physiol 290:H1549–H1557. https://doi.org/10.1152/ajpheart.00913.2005
Marques-Aleixo I, Oliveira PJ, Moreira PI et al (2012) Physical exercise as a possible strategy for brain protection: evidence from mitochondrial-mediated mechanisms. Prog Neurobiol 99:149–162. https://doi.org/10.1016/j.pneurobio.2012.08.002
Marques-Aleixo I, Santos-Alves E, Balça MM et al (2015a) Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers. Neuroscience 301:480–495. https://doi.org/10.1016/j.neuroscience.2015.06.027
Marques-Aleixo I, Santos-Alves E, Mariani D et al (2015b) Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress. Mitochondrion 20:22–33. https://doi.org/10.1016/j.mito.2014.10.008
Marques-Aleixo I, Santos-Alves E, Balça MM et al (2016) Physical exercise mitigates doxorubicin-induced brain cortex and cerebellum mitochondrial alterations and cellular quality control signaling. Mitochondrion 26:43–57. https://doi.org/10.1016/j.mito.2015.12.002
Matiello R, Fukui RT, Silva ME et al (2010) Differential regulation of PGC-1alpha expression in rat liver and skeletal muscle in response to voluntary running. Nutr Metab (Lond) 7:36. https://doi.org/10.1186/1743-7075-7-36
McGee SL, Fairlie E, Garnham AP, Hargreaves M (2009) Exercise-induced histone modifications in human skeletal muscle. J Physiol 587:5951–5958. https://doi.org/10.1113/jphysiol.2009.181065
Morgan MJ, Liu Z (2011) Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res 21:103–115. https://doi.org/10.1038/cr.2010.178
Mottillo EP, Desjardins EM, Crane JD et al (2016) Lack of adipocyte AMPK exacerbates insulin resistance and hepatic steatosis through Brown and Beige adipose tissue function. Cell Metab 24:118–129. https://doi.org/10.1016/j.cmet.2016.06.006
Musman J, Pons S, Barau C et al (2016) Regular treadmill exercise inhibits mitochondrial accumulation of cholesterol and oxysterols during myocardial ischemia-reperfusion in wild-type and ob/ob mice. Free Radic Biol Med 101:317–324. https://doi.org/10.1016/j.freeradbiomed.2016.10.496
Norheim F, Langleite TM, Hjorth M et al (2014) The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J 281:739–749. https://doi.org/10.1111/febs.12619
Ost M, Coleman V, Kasch J, Klaus S (2016) Regulation of myokine expression: role of exercise and cellular stress. Free Radic Biol Med 98:78–89. https://doi.org/10.1016/j.freeradbiomed.2016.02.018
Pagano AF, Py G, Bernardi H et al (2014) Autophagy and protein turnover signaling in slow-twitch muscle during exercise. Med Sci Sports Exerc 46:1314–1325. https://doi.org/10.1249/MSS.0000000000000237
Pareja-Galeano H, Sanchis-Gomar F, García-Giménez JL (2014) Physical exercise and epigenetic modulation: elucidating intricate mechanisms. Sport Med 44:429–436. https://doi.org/10.1007/s40279-013-0138-6
Park J-W, Kim M-H, Eo S-J et al (2013) Maternal exercise during pregnancy affects mitochondrial enzymatic activity and biogenesis in offspring brain. Int J Neurosci 123:253–264. https://doi.org/10.3109/00207454.2012.755969
Pedersen BK, Saltin B (2015) Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 25:1–72. https://doi.org/10.1111/sms.12581
Pedersen BK, Steensberg A, Fischer C et al (2003) Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil 24:113–119
Perry CGR, Lally J, Holloway GP et al (2010) Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol 588:4795–4810. https://doi.org/10.1113/jphysiol.2010.199448
Pessayre D, Mansouri A, Berson A, Fromenty B (2010) Mitochondrial involvement in drug-induced liver injury. Handb Exp Pharmacol 196:311–365
Powers SK, Smuder AJ, Kavazis AN, Quindry JC (2014a) Mechanisms of exercise-induced cardioprotection. Physiology 29:27–38. https://doi.org/10.1152/physiol.00030.2013
Powers SK, Sollanek KJ, Wiggs MP et al (2014b) Exercise-induced improvements in myocardial antioxidant capacity: the antioxidant players and cardioprotection. Free Radic Res 48:43–51. https://doi.org/10.3109/10715762.2013.825371
Puigserver P, Rhee J, Lin J et al (2001) Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell 8:971–982
Quindry JC, Schreiber L, Hosick P et al (2010) Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts. Am J Physiol Heart Circ Physiol 299:H175–H183. https://doi.org/10.1152/ajpheart.01211.2009
Radak Z, Ishihara K, Tekus E et al (2017) Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve. Redox Biol 12:285–290. https://doi.org/10.1016/j.redox.2017.02.015
Rector RS, Thyfault JP (2011) Does physical inactivity cause nonalcoholic fatty liver disease? J Appl Physiol 111:1828–1835. https://doi.org/10.1152/japplphysiol.00384.2011
Reid MB, Khawli FA, Moody MR (1993) Reactive oxygen in skeletal muscle. III. Contractility of unfatigued muscle. J Appl Physiol 75:1081–1087
Ristow M, Zarse K, Oberbach A et al (2009) Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A 106:8665–8670. https://doi.org/10.1073/pnas.0903485106
Rocha-Rodrigues S, Rodríguez A, Gouveia AM et al (2016) Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Sci 165:100–108. https://doi.org/10.1016/j.lfs.2016.09.023
Rocha-Rodrigues S, Rodríguez A, Becerril S et al (2017) Physical exercise remodels visceral adipose tissue and mitochondrial lipid metabolism in rats fed a high-fat diet. Clin Exp Pharmacol Physiol 44:386–394. https://doi.org/10.1111/1440-1681.12706
Rodas G, Ventura JL, Cadefau JA et al (2000) A short training programme for the rapid improvement of both aerobic and anaerobic metabolism. Eur J Appl Physiol 82:480–486. https://doi.org/10.1007/s004210000223
Roh J, Rhee J, Chaudhari V, Rosenzweig A (2016) The role of exercise in cardiac aging. Circ Res 118:279–295. https://doi.org/10.1161/CIRCRESAHA.115.305250
Ruderman NB, Xu XJ, Nelson L et al (2010) AMPK and SIRT1: a long-standing partnership? Am J Physiol Endocrinol Metab 298:E751–E760. https://doi.org/10.1152/ajpendo.00745.2009
Russell AP, Lamon S (2015) Exercise, skeletal muscle and circulating microRNAs. Prog Mol Biol Transl Sci 135:471–496
Safdar A, Bourgeois JM, Ogborn DI et al (2011) Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proc Natl Acad Sci 108:4135–4140. https://doi.org/10.1073/pnas.1019581108
Safdar A, Khrapko K, Flynn JM et al (2015) Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice. Skelet Muscle 6:7. https://doi.org/10.1186/s13395-016-0075-9
Saleem A, Hood DA (2013) Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53-Tfam-mitochondrial DNA complex in skeletal muscle. J Physiol 591:3625–3636. https://doi.org/10.1113/jphysiol.2013.252791
Saleem A, Adhihetty PJ, Hood DA (2009) Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle. Physiol Genomics 37:58–66. https://doi.org/10.1152/physiolgenomics.90346.2008
Santos-Alves E, Marques-Aleixo I, Coxito P et al (2014) Exercise mitigates diclofenac-induced liver mitochondrial dysfunction. Eur J Clin Investig 44:668–677. https://doi.org/10.1111/eci.12285
Santos-Alves E, Marques-Aleixo I, Rizo-Roca D et al (2015) Exercise modulates liver cellular and mitochondrial proteins related to quality control signaling. Life Sci 135:124–130. https://doi.org/10.1016/j.lfs.2015.06.007
Scarpulla RC (2011) Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 1813:1269–1278. https://doi.org/10.1016/j.bbamcr.2010.09.019
Schantz P, Henriksson J, Jansson E (1983) Adaptation of human skeletal muscle to endurance training of long duration. Clin Physiol 3:141–151
Schantz PG, Sjoberg B, Svedenhag J (1986) Malate-aspartate and alpha-glycerophosphate shuttle enzyme levels in human skeletal muscle: methodological considerations and effect of endurance training. Acta Physiol Scand 128:397–407. https://doi.org/10.1111/j.1748-1716.1986.tb07993.x
Schnyder S, Handschin C (2015) Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. Bone 80:115–125. https://doi.org/10.1016/j.bone.2015.02.008
Schwerzmann K, Hoppeler H, Kayar SR, Weibel ER (1989) Oxidative capacity of muscle and mitochondria: correlation of physiological, biochemical, and morphometric characteristics. Proc Natl Acad Sci 86:1583–1587. https://doi.org/10.1073/pnas.86.5.1583
Scott HA, Latham JR, Callister R et al (2015) Acute exercise is associated with reduced exhaled nitric oxide in physically inactive adults with asthma. Ann Allergy Asthma Immunol 114:470–479. https://doi.org/10.1016/j.anai.2015.04.002
Simon H-U, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5:415–418. https://doi.org/10.1023/A:1009616228304
Siu PM, Bryner RW, Martyn JK, Alway SE (2004) Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J 18:1150–1152. https://doi.org/10.1096/fj.03-1291fje
Smuder AJ, Kavazis AN, Min K, Powers SK (2013) Doxorubicin-induced markers of myocardial autophagic signaling in sedentary and exercise trained animals. J Appl Physiol 115:176–185. https://doi.org/10.1152/japplphysiol.00924.2012
Soriano FX, Liesa M, Bach D et al (2006) Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor- coactivator-1, estrogen-related receptor-, and mitofusin 2. Diabetes 55:1783–1791. https://doi.org/10.2337/db05-0509
Stallknecht B, Vinten J, Ploug T, Galbo H (1991) Increased activities of mitochondrial enzymes in white adipose tissue in trained rats. Am J Phys 261:E410–E414
Stanford KI, Middelbeek RJW, Goodyear LJ (2015) Exercise effects on white adipose tissue: beiging and metabolic adaptations. Diabetes 64:2361–2368. https://doi.org/10.2337/db15-0227
Steiner JL, Murphy EA, McClellan JL et al (2011) Exercise training increases mitochondrial biogenesis in the brain. J Appl Physiol 111:1066–1071. https://doi.org/10.1152/japplphysiol.00343.2011
St-Pierre J, Drori S, Uldry M et al (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408. https://doi.org/10.1016/j.cell.2006.09.024
Suen D-F, Norris KL, Youle RJ (2008) Mitochondrial dynamics and apoptosis. Genes Dev 22:1577–1590. https://doi.org/10.1101/gad.1658508
Sun M, Huang C, Wang C et al (2013) Ginsenoside Rg3 improves cardiac mitochondrial population quality: mimetic exercise training. Biochem Biophys Res Commun 441:169–174. https://doi.org/10.1016/j.bbrc.2013.10.039
Sutherland LN, Bomhof MR, Capozzi LC et al (2009) Exercise and adrenaline increase PGC-1α mRNA expression in rat adipose tissue. J Physiol 587:1607–1617. https://doi.org/10.1113/jphysiol.2008.165464
Taanman J-W (1999) The mitochondrial genome: structure, transcription, translation and replication. Biochim Biophys Acta Bioenerg 1410:103–123. https://doi.org/10.1016/S0005-2728(98)00161-3
Taghizadeh G, Pourahmad J, Mehdizadeh H et al (2016) Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment. Free Radic Biol Med 99:11–19. https://doi.org/10.1016/j.freeradbiomed.2016.07.018
Talanian JL, Holloway GP, Snook LA et al (2010) Exercise training increases sarcolemmal and mitochondrial fatty acid transport proteins in human skeletal muscle. Am J Physiol Endocrinol Metab 299:E180–E188. https://doi.org/10.1152/ajpendo.00073.2010
Terblanche SE, Gohil K, Packer L et al (2001) The effects of endurance training and exhaustive exercise on mitochondrial enzymes in tissues of the rat (Rattus norvegicus). Comp Biochem Physiol A Mol Integr Physiol 128:889–896
Thyfault JP, Rector RS, Uptergrove GM et al (2009) Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury. J Physiol 587:1805–1816. https://doi.org/10.1113/jphysiol.2009.169060
Townsend LK, Knuth CM, Wright DC (2017) Cycling our way to fit fat. Physiol Rep 5:e13247. https://doi.org/10.14814/phy2.13247
Trevellin E, Scorzeto M, Olivieri M et al (2014) Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes 63:2800–2811. https://doi.org/10.2337/db13-1234
Vainshtein A, Kazak L, Hood DA (2011) Effects of endurance training on apoptotic susceptibility in striated muscle. J Appl Physiol 110:1638–1645. https://doi.org/10.1152/japplphysiol.00020.2011
Vainshtein A, Tryon LD, Pauly M, Hood DA (2015) Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am J Physiol Cell Physiol 308:C710–C719. https://doi.org/10.1152/ajpcell.00380.2014
Wang C, Youle RJ (2009) The role of mitochondria in apoptosis. Annu Rev Genet 43:95–118. https://doi.org/10.1146/annurev-genet-102108-134850
Wei Y, Rector RS, Thyfault JP, Ibdah JA (2008) Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J Gastroenterol 14:193–199
Westermann B (2012) Bioenergetic role of mitochondrial fusion and fission. Biochim Biophys Acta Bioenerg 1817:1833–1838. https://doi.org/10.1016/j.bbabio.2012.02.033
Whelan RS, Konstantinidis K, Wei A-C et al (2012) Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci 109:6566–6571. https://doi.org/10.1073/pnas.1201608109
White Z, Terrill J, White RB et al (2016) Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice. Skelet Muscle 6:45. https://doi.org/10.1186/s13395-016-0117-3
Wright DC, Geiger PC, Han D-H et al (2007) Calcium induces increases in peroxisome proliferator-activated receptor coactivator-1 and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation. J Biol Chem 282:18793–18799. https://doi.org/10.1074/jbc.M611252200
Xu Y, Zhao C, Sun X et al (2015) MicroRNA-761 regulates mitochondrial biogenesis in mouse skeletal muscle in response to exercise. Biochem Biophys Res Commun 467:103–108. https://doi.org/10.1016/j.bbrc.2015.09.113
Xu WH, Wu H, Xia WL et al (2016) Physical exercise before pregnancy helps the development of mouse embryos produced in vitro. Mitochondrion. https://doi.org/10.1016/j.mito.2016.12.004
Yamamoto H, Morino K, Nishio Y et al (2012) MicroRNA-494 regulates mitochondrial biogenesis in skeletal muscle through mitochondrial transcription factor A and Forkhead box j3. AJP Endocrinol Metab 303:E1419–E1427. https://doi.org/10.1152/ajpendo.00097.2012
Yu T, Robotham JL, Yoon Y (2006) Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci U S A 103(8):2653. https://doi.org/10.1073/pnas.0511154103
Zampieri S, Mammucari C, Romanello V et al (2016) Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics. Physiol Rep 4(24):e13005. https://doi.org/10.14814/phy2.13005
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Beleza, J., Rizo-Roca, D., Ascensão, A., Magalhães, J. (2018). Targeting Mitochondria with Sweat: Improving Mitochondrial Function with Physical Activity. In: Oliveira, P. (eds) Mitochondrial Biology and Experimental Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-73344-9_18
Download citation
DOI: https://doi.org/10.1007/978-3-319-73344-9_18
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-73343-2
Online ISBN: 978-3-319-73344-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)