Abstract
Endurance training is a widely practised physical exercise modality aimed at increasing the aerobic working capacity. This review discusses the current state-of-the-art in research on the mechanisms of the exercise-induced quantitative and qualitative alterations in mitochondrial biogenesis and intracellular energy transfer in cardiac and skeletal muscle cells. The data show that endurance training exerts a permissive effect on biogenesis of mitochondria through stimulating multiple pathways converging at activation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). These pathways are mediated by stress hormones (glucocorticoids and catecholamines), p38 mitogen-activated protein kinase (MAPK), class III histone deacylases (SIRT1 and SIRT3), cyclic nucleotide regulatory binding protein (CREB), p53 tumor suppressor protein, and AMP-activated protein kinase (AMPK). As a result, oxidative capacity of cardiac and skeletal muscle cells increases to cope with enhanced ATP turnover. In parallel, exercise induces significant changes in intrinsic properties of mitochondria expressed as suppressed capacity to produce ROS and resistance to permeability transition and apoptotic signals. These effects of training enable to protect myocardium by attenuating the decay in cardiac function in conditions of ischemic heart disease, heart failure, diabetes, and obesity. The beneficial effects of endurance training disappear in conditions of application of excessive training volumes which results in overtraining syndrome (OTS) characterized by skeletal and cardiac muscle damage and suppression of oxidative energy metabolism. Therefore, establishing criteria for early detection of development of OTS to avoid associated harmful impact on organism is of ultimate importance.
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References
Braun LT (1991) Exercise physiology and cardiovascular fitness. Nurs Clin North Am 26:135–147
Steinacker J, Kellmann M, Böhm B, Liu Y, Opitz-Gress A, Kallus K, Lehmann M, Altenburg D, Lormes W (1999) Clinical findings and parameters of stress and regeneration in rowers before world championships. In: Lehmann M, Foster C, Gastmann U, Keizer H, Steinacker J (eds) Overload, performance incompendence, and regeneration in sport. Kluwer Academic/Plenum Publishers, New York, pp 71–80
Hardie DG, Sakamoto K (2006) AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology 21:48–60
Stepto N, Martin D, Fallon K, Hawley J (2001) Metabolic demands of intense aerobic interval training in competitive cyclists. Med Sci Sports Exerc 33:303–310
Yeo WK, Paton CD, Garnham AP et al (2008) Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens. J Appl Physiol 105:1462–1470
van Wessel T, de Haan A, van der Laarse WJ, Jaspers RT (2010) The muscle fiber type-fiber size paradox: hypertrophy or oxidative metabolism. Eur J Appl Physiol 110:665–694
Navarro A, Gomez C, López-Cepero JM, Boveris A (2004) Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer. Am J Physiol Regul Integr Comp Physiol 286:505–511
Boveris A, Navarro A (2008) Systemic and mitochondrial adaptive responses to moderate exercise in rodents. Free Rad Biol Med 44:224–229
Halson SL, Jeukendrup AE (2004) Does overtaining exist? An analysis of overreaching and overtraining research. Sports Med 34:967–981
Meeusen R, Watson P, Hasegawa H et al (2007) Brain neurotransmitters in fatigue and overtraining. Appl Physiol Nutr Metab 32:857–864
Steinacker JM, Lormes W, Reissnecker S, Liu Y (2004) New aspects of the hormone and cytokine response to training. Eur J Appl Physiol 91:382–391
Hohl R, Ferraresso RL, De Oliveira RB et al (2009) Development and characterization of an overtraining animal model. Med Sci Sports Exerc 41:1155–1163
Kaasik P, Seene T (2010) The overtraining syndrome: reflection in skeletal muscle. Gazz Med Ital—Arch Sci Med 169:311–319
Seene T, Umnova M, Kaasik P, Alev K, Pehme A (2008) Overtraining injuries in athletic population. In: Tiidus PM (ed) Skeletal muscle damage and repair. Windsor, Human Kinetics, pp 173–184
Sahlin K, Tonkonogi M, Söderlund K (1998) Energy supply and muscle fatique in humans. Acta Physiol Scand 162:261–266
Manoli I, Alesci S, Blackman MR et al (2007) Mitochondria as key components of the stress response. Trends Endocrinol Metab 18:190–198
Mastorakos G, Pavlatou M, Diamanti-Kandarakis E, Chrousos GP (2005) Exercise and the stress system. Hormones 4:73–89
Scheller K, Sekeris CE (2003) The effects of steroid hormones on the transcription of genes encoding enzymes of oxidative phosphorylation. Exp Physiol 88:129–140
Seppet EK, Kaambre T, Sikk P et al (2001) Functional complexes of mitochondria with Ca, MgATPases of myofibrils and sarcoplasmic reticulum in muscle cells. Biochim Biophys Acta 504:379–395
Saks VA, Kaambre T, Sikk P et al (2001) Intracellular energetic units in red muscle cells. Biochem J 356:643–657
Anmann T, Eimre M, Kuznetsov AV et al (2006) Structure-function relationships in the regulation of energy transfer between mitochondria and ATPases in cardiac cells. Exp Clin Cardiol 1:189–194
Singh A, Petrides JS, Gold OW, Chrousos GP et al (1999) Differential hypothalamic–pituitary–adrenal axis reactivity to psychological and physical stress. J Clin Endocrinol Metab 84:1944–1948
Jürimäe J, Mäestu J, Jürimäe T et al (2011) Peripheral signals of energy homeostasis as possible markers of training stress in athlete: a review. Metabolism 60:335–350
Sellers TL, Jaussi AW, Yang HT et al (1988) Effect of the exercise induced increase in glucocorticoids on endurance in rat. J Appl Physiol 65:173–178
Tharp GD (1975) The role of glucocorticoids in exercise. Med Sci Sports Exerc 7:6–11
Wilmore JH, Costill DL (1994) Hormonal regulation of exercise. In: Wilmore JH, Costill DL (eds) Physiology of sport and exercise. Human Kinetics, Champaign, pp 1–549
Zanesco A, Antunes E (2007) Effects of exercise training on the cardiovascular system: pharmacological approaches. Pharmacol Ther 114:307–317
Birnbaumer L (1990) G proteins in signal transduction. Annu Rev Pharmacol Toxicol 30:675–705
Korzick DH (2003) Regulation of cardiac exitation–contraction coupling: a cellular update. Adv Physiol Educ 27:192–200
Lands AM, Arnold A, McAuliff JP et al (1967) Differentiation of receptors systems activated by sympatomimetic amines. Nature 214:498–597
Kubo T, Fukuda K, Mikami A et al (1986) Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature 232:411–416
Ekblom B, Kilblom A, Soltysiak J (1973) Physical training, bradycardia, and autonomic nervous system. J Clin Lab Invest 32:251–256
Tulppo MP, Mäkikallio TH, Seppänen T et al (1998) Vagal modulation of heart rate during exercise: effects of age and physical fitness. Am J Physiol 274(2):424–429
Levy WC, Cerqueira MD, Harp GD et al (1998) Effect of endurance exercise training on heart rate variability at rest in healthy young and older men. Am J Cardiol 82:1236–1241
Billman GE (2002) Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention. J Appl Physiol 92:446–454
Kiviniemi AM, Hautala AJ, Makikallio TH et al (2006) Cardiac vagal outflow after aerobic training by analysis of high frequency oscillation of the R–R interval. Eur J Appl Physiol 96:686–692
Hautala AJ, Kiviniemi AM, Tulppo MP (2009) Individual responses to aerobic exercise: the role of the autonomic nervous system. Neurosci Biobehav Rev 33:107–115
Moncada S, Palmer RM, Higgs EA (1991) Nitric oxide physiology and pharmacology. Pharmacol Rev 43:109–142
Traub O, Berk BC (1998) Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol 18:677–685
Seddon M, Shah AM, Casadei B (2007) Cardiomyocytes as effectors of nitric oxide signalling. Cardiovasc Res 75:315–326
Brown GC, Borutaite V (2007) Nitric oxide and mitochondrial respiration in the heart. Cardiovasc Res 75:283–290
Casadei B, Sears CE (2003) Nitric-oxide-mediated regulation of cardiac contractility and stretch responses. Progr Biophys Mol Biol 82:67–80
Dedkova EN, Blatter LA (2009) Characteristics and function of cardiac mitochondrial nitric oxide synthase. J Physiol 587:851–872
Nisoli E, Carruba MO (2006) Nitric oxide and mitochondrial biogenesis. J Cell Sci 119:2855–2862
Demirel HA, Powers SK, Zergeroglu MA et al (2001) Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. J Appl Physiol 91:2205–2212
Brown GC (2001) Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta 1504:46–57
Pedram G, Sen CK (2007) Mitochondrial nitric oxide synthase. Front Biosci 12:1072–1078
Zhang JS, Kraus WE, Truskey GA (2004) Stretch-induced nitric oxide modulates mechanical properties of skeletal muscle cells. Am J Physiol Cell Physiol 287:292–299
Mohan RM, Choate JK, Golding S et al (2000) Peripheral pre-synaptic pathway reduces the heart rate response to sympathetic activation fillowing exercise training: role of NO. Cardiovasc Res 47:90–98
Kim YM, Talanian RV, Billiar TR (1997) Nitric oxide inhibits apoptosis by preventing increases in caspase-3-like activity via two distinct mechanisms. J Biol Chem 272:31138–31148
Xu Q, Hu Y, Kleindienst R, Wick G (1997) Nitric oxide induces heat-shock protein 70 expression in vascular smooth muscle cells via activation of heat shock factor 1. J Clin Invest 100:1089–1097
Suwaidi JA, Hamasaki S, Higano ST et al (2000) Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 101:948–954
Neunteufl T, Heher S, Katzenschlager R et al (2000) Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 86:207–210
Lemström KB, Krebs R, Nykänen AI et al (2002) Vascular endothelial growth factor enhances cardiac allograft arteriosclerosis. Circulation 105:2524–2530
Richardson RS, Wagner H, Mudaliar SR et al (2000) Exercise adaptation attenuates VEGF gene expression in human skeletal muscle. Am J Physiol Heart Circ Physiol 279:772–778
Droge W (2002) Free radicals in the physiological control of cell function. Physiol Res 82:47–95
Calvert JW (2011) Cardioprotective effects of nitrite during exercise. Cardiovasc Res 89:499–506
Ribeiro JA, Sebastiäo AM (1986) Adenosine receptors and calcium: Basis for proposing a third A3 adenosin receptor. Prog Neurobiol 26:179–209
Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55
McIntosh VJ, Lasley RD (2012) Adenosine receptor-mediated cardioprotection: are all 4 subtypes required or redundant? J Cardiovasc Pharmacol Ther 17:21–33
Noble EG, Moraska A, Mazzeo RS et al (1999) Differential expression of stress proteins in rat myocardium after free wheel or treadmill run training. J Appl Physiol 86:1696–1701
Ascensão A, Magalhães J, Soares JM et al (2006) Endurance training limits the functional alterations of heart rat mitochondria submitted to in vitro anoxia-reoxygenation. Int J Cardiol 109:169–178
Watson PA, Reusch JEB, McCune SA et al (2007) Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise. Am J Physiol Heart Circ Physiol 293:246–259
Marcil M, Bourduas K, Ascah A, Burelle Y (2006) Exercise training induces respiratory substrate-specific decrease in Ca2+-induced permeability transition pore opening in heart mitochondria. Am J Physiol Heart Circ Physiol 290:1549–1557
Bernardo BC, Weeks KL, Pretorius L, McMullen JR (2010) Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies. Pharmacol Ther 128:191–227
Evangelista FS, Brum PC, Krieger JE (2003) Duration-controlled swimming exercise training induces cardiac hypertrophy in mice. Braz J Med Biol Res 36:1751–1759
Powers SK, Demirel HA, Vincent HK et al (1998) Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. Am J Physiol Regul Integr Comp Physiol 275:1468–1477
Kayar SR, Conley KE, Claassen H, Hoppeler H (1986) Capillarity and mitochondrial distribution in rat myocardium following exercise training. J Exp Biol 120:189–199
Lehman JJ, Kelly DP (2002) Gene regulatory mechanisms governing energy metabolism during cardiac hypertrophic growth. Heart Failure Rev 7:175–185
Van der Vusse GJ, Glatz JF, Stam HC, Reneman RS (1992) Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev 72:881–940
Blomstrand E, Ekblom B, Newsholme EA (1986) Maximum activities of key glycolytic and oxidative enzymes in human muscle from differently trained individuals. J Physiol 381:111–118
Green HJ, Reichmann H, Pette D (1983) Fibre type specific transformations in the enzyme activity pattern of rat vastus lateralis muscle by prolonged endurance training. Pflugers Arch 399:216–222
Matsakas A, Macharia R, Otto A et al (2012) Exercise training attenuates the hypermuscular phenotype and restores skeletal muscle function in the myostatin null mouse. Exp Physiol 97:125–140
Wikman-Coffelt J, Parmley WW, Mason DT (1979) The cardiac hypertrophy process. Analyses of factors determining pathological vs physiological development. Circ Res 45:697–707
Rupp H (1981) The adaptive changes in the isoenzyme pattern of myosin from hypertrophied rat myocardium as a result of pressure overload and physical training. Basic Res Cardiol 76:79–88
Pierce GN, Sekhon PS, Meng HP, Maddaford TG (1989) Effects of chronic swimming training on cardiac sarcolemmal function and composition. J Appl Physiol 66:1715–1721
Jin H, Yang R, Li W et al (2000) Effects of exercise on cardiac function, gene expression and apoptosis in rats. Am Physiol Heart Circ Physiol 279:2994–3002
Pagani ED, Solaro RJ (1983) Swimming exercise, thyroid state, and the distribution of myosin isoenzymes in rat heart. Am J Physiol Heart Circ Physiol 245:713–720
Wisloff U, Loennechen JP, Falck G et al (2001) Increased conractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats. Cardiovasc Res 50:495–508
Diffee GM, Seversen EA, Stein TD, Johnson JA (2003) Microarray expression analysis of effects of exercise training: increase in atrial MLC-1 in rat ventricles. Am J Physiol Heart Circ Physiol 284:830–837
Tate CA, Helgason T, Hyek MF et al (1996) SERCA2a and mitochondrial cytochrome oxidase are increased in hearts of exercise-trained old rats. Am J Physiol 271:68–72
Malhotra A, Penpargkul S, Schaible T, Scheuer J (1981) Contractile proteins and sarcoplasmic reticulum in physiologic cardiac hypertrophy. Am J Physiol 241:263–267
Buttrick PM, Kaplan M, Leinwand LA, Scheuer J (1994) Alterations in gene expression in the rat heart after chronic pathological ad physiological loads. J Mol Cell Cardiol 26:61–67
Bottinelli R (2001) Functional heterogeneity of mammalian single muscle fibres: do myosin isoforms tell the whole story? Pflugers Arch 443:6–17
Nuhr M, Crevenna R, Gohlsch B et al (2003) Functional and biochemical properties of chronically stimulated human skeletal muscle. Eur J Appl Physiol 89:202–208
Thayer R, Collins J, Noble EG, Taylor AW (2000) A decade of aerobic endurance training: histological evidence for fibre type transformation. J Sports Med Phys Fitness 40:284–289
Baldwin KM, Haddad F (2001) Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. J Appl Physiol 90:345–357
Mohr M, Krustrup P, Nielsen JJ et al (2007) Effect of two different intense training regimes on skeletal muscle ion transport proteins and fatigue development. Am J Physiol 292:1594–1602
Ljubicic V, Joseph A-M, Saleem A et al (1800) Transcriptional and post-transcriptional regulation of mitochondrial biogenesis in skeletal muscle: effect of exercise and aging. Biochim Biophys Acta 223–234:2010
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
Baldwin KM, Klinkerfuss GH, Terjung RL et al (1972) Respiratory capacity of white, red, and intermediate muscle: adaptative response to exercise. Am J Physiol 222:373–378
Dudley GA, Tullson PC, Terjung RL (1987) Influence of mitochondrial content on the sensitivity of respiratory control. J Biol Chem 262:9109–9114
Holloszy JO, Booth FW (1976) Biochemical adaptation to endurance exercise in muscle. Annu Rev Physiol 38:273–291
Davies KJ, Packer L, Brooks GA (1981) Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training. Arch Biochem Biophys 209:539–554
Venditti P, Masullo P, Di Meo S (1999) Effect of training on H2O2 release by mitochondria from rat skeletal muscle. Arch Biochem Biopys 372:315–320
Hood DA (2001) Contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 90:1137–1157
Hood DA (2009) Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Appl Physiol Nutr Metab 34:465–472
Little JP, Safdar A, Wilikin GP et al (2010) A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. J Physiol 588:1011–1022
Menshikova EV, Ritov VB, Fairfull L et al (2006) Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci 61:534–540
Menshikova EV, Ritov VB, Ferrell RE et al (2007) Characteristic of skeletal muscle mitochondrial biogenesis induced by moderate-intensity exercise and weight loss in obesity. J Appl Physiol 103:21–27
Molnar AM, Alves AA, Pereira-da-Silva L et al (2004) Evaluation by blue native polyacrylamide electrophoresis colorimetric staining of the effects of physical exercise on the activities of mitochondrial complexes in rat muscle. Braz J Med Biol Res 37:939–947
Tyler CM, Golland LC, Evans DL et al (1998) Skeletal muscle adaptations to prolonged training, overtraining and detraining in horses. Pflügers Arch—Eur J Physiol 436:391–397
Silva LA, Pinho CA, Scarabelot KS et al (2009) Physical exercise increases mitochondrial function and reduces oxidative damage in skeletal muscle. Eur J Appl Physiol 105:861–867
Spina RJ, Chi MM, Hopkins MG et al (1996) Mitochondrial enzymes increase in muscle in response to 7–10 days of cycle exercise. J Appl Physiol 80:2250–2254
Coleman R, Weiss A, Finkelbrand S, Silbermann M (1988) Age and exercise-related changes in myocardial mitochondria in mice. Acta Histochem 83:81–90
Stuewe SR, Gwirtz PA, Agarwal N, Mallet RT (2000) Exercise training enhances glycolytic and oxidative enzymes in canine ventricular myocardium. J Mol Cell Cardiol 32:903–913
Sun B, Wang JH, Lv YY et al (2008) Proteomic adaptation to chronic high intensity swimming training in the rat heart. Comp Biochem Physiol 3:108–117
Baldwin KM, Cooke DA, Cheadle WG (1977) Time course adaptations in cardiac and skeletal muscle to different running programs. J Appl Physiol 42:267–272
Oscai LB, Molé PA, Holloszy JO (1971) Effects of exercise on cardiac weight and mitochondria in male and female rats. Am J Physiol 220:1944–1948
Kemi OJ, Høydal MA, Haram PM et al (2007) Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan. Cardiovasc Res 76:91–99
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
Bozner A, Meessen H (1969) The ultrastructure of the myocardium of the rat after single and repeated swim exercises. Virchows Arch B Cell Pathol 3:248–269
Anversa P, Beghi C, Levicky V et al (1982) Morphometry of right ventricular hypertrophy induced by strenuous exercise in rat. Am J Physiol 243:856–861
Paniagua R, Vázques JJ, López-Moratalla N (1977) Effects of physical training on rat myocardium. An enzymatic and ultrastructural morphometric study. Rev Esp Fisiol 33:273–281
Eisele JC, Schaefer I-M, Nyengaard JR et al (2008) Effect of voluntary exercise on number and volume of cardiomyocytes and their mitochondria in the mouse left ventricle. Basic Res Cardiol 103:12–21
Betik AC, Thomas MM, Wright KJ et al (2009) Exercise training from late middle age until senescence does not attenuate the declines in skeletal muscle aerobic function. Am J Physiol Integr Comp Physiol 297:744–755
Konhilas JP, Mass AH, Luckey SW et al (2004) Sex modifies exercise and cardiac adaptation in mice. Am J Physiol Heart Circ Physiol 287:2768–2776
Laguens RP, Gómez-Dumm CLA (1967) Fine-structure of myocardial mitochondria in rats after exercise for one-half to two hours. Circ Res 21:271–279
Gleyzer N, Vercauteren K, Scarpulla RC (2005) Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NFR-2) and PGC-1 family coactivators. Mol Cell Biol 25:1354–1366
Scarpulla RC (2006) Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 97:673–683
Akimoto T, Pohnert SC, Li P et al (2005) Exercise stimulates PGC-1a transcription in skeletal muscle through activation of the p38 MAPK pathway. J Biol Chem 280:19587–19593
Pogozelski AR, Geng T, Li P et al (2009) p38γ mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice. PloS ONE 4: Article ID e7934
Knutti D, Kessler D, Kralli A (2001) Regulation of the trasncriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor. Proc Natl Acad Sci U S A 98:9713–9718
Fan M, Rhee J, St-Pierre J et al (2004) Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1: modulation by p38 MAPK. Genes Dev 18:278–289
Puigserver P, Rhee J, Lin J et al (2001) Cytokine stimulation of enenrgy expenditure through p38 MAP kinase activation of PPAR gamma coactivator-1. Mol Cell 8:971–982
Lee WJ, Kim M, Park HS et al (2006) AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPAR alpha and PGC-1. Biochem Biophys Res Commun 340:291–295
Narkar VA, Downes M, Yu RT et al (2008) AMPK and PPAR delta agonists are exercise mimetics. Cell 134:1–11
Menzies KJ, Hood DA (2012) The role of SirT1 in muscle mitochondrial turnover. Mitochondrion 12:5–13
Amat R, Planavila A, Chen SL et al (2009) SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-gamma Co-activator-1alpha (PGC-1alpha) gene in skeletal muscle through the PGC-1alpha autoregulatory loop and interaction with MyoD. J Biol Chem 284:21872–21880
Dumke CL, Davis JM, Murphy EA et al (2009) Successive bouts of cucling stimulates genes associated with mitocondrial biogenesis. Eur J Appl Physiol 107:419–427
Pillai VB, Sundaresan NR, Jeevanandam V, Gupta MP (2010) Mitochondrial SIRT3 and heart disease. Cardiovasc Res 88:250–256
Gurd BJ, Holloway GP, Yoshida Y, Bonen A (2011) In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate-activated protein kinase-independent manner. Metabolism 9:1–9
Palacios OM, Carmona JJ, Michan S et al (2009) Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging 1:771–783
Hokary F, Kawasaki E, Sakai A et al (2010) Muscle contractile activity regulates Sirt3 protein expression in rat skeletal muscles. J Appl Physiol 109:332–340
Wu Z, Huang X, Feng Y et al (2006) Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1α transcription and mitochondrial biogenesis in muscle cells. Proc Natl Acad Sci U S A 103:14379–14384
Matoba S, Kang JG, Patino WD et al (2006) P53 regulates mitochondrial respiration. Science 312:1650–1653
Achanta G, Sasaki R, Feng L et al (2005) Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma. EMBO J 24:3482–3492
Yoshida Y, Izumi H, Torigoe T et al (2003) P53 physically intyeracts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA. Cancer Res 63:3729–3734
Park J-Y, Wang P-Y, Matsumoto T et al (2009) P53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res 105:705–712
Saleem A, Adhietty PJ, Hood DA (2009) Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscles. Physiol Genomics 37:58–66
Qi Z, He J, Su Y et al (2011) Physical exercise regulated p53 activity targeting SCO2 and increases mitochondrial biogenesis in cardiac muscle with age. PLoS One 6:e21140
Starnes JW, Barnes BD, Olsen M (2007) Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction. J Appl Physiol 102:1793–1798
Navarro A, Gomez C, López-Cepero JM, Boveris A (2004) Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer. Am J Physiol Regul Integr Comp Physiol 286:505–511
Judge S, Jang YM, Smith A et al (2005) Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart. Am J Physiol Regul Integr Comp Physiol 289:1564–1572
Bo H, Jiang N, Ma G et al (2008) Regulation of mitochondrial uncoupling respiration during exercise in rat heart: role of reactive oxygen species (ROS) and uncoupling protein 2. Free Rad Biol Med 44:1373–1381
Bizeau ME, Willis WT, Hazel JR (1998) Differential responses to endurance training in subsarcolemmal and intermyofibrillar mitochondria. J Appl Physiol 85:1279–1284
Starritt EC, Angus D, Hargreaves M (1999) Effect of short-term training on mitochondrial ATP production rate in human skeletal muscle. J Appl Physiol 86:450–454
Fernström M, Tonkonogi M, Sahlin K (2003) Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle. J Physiol 554:755–763
Kuznetsov AV, Tiivel T, Sikk P et al (1996) Striking differences between the kinetics of regulation of respiration by ADP in slow-twitch and fast-twitch muscles in vivo. Eur J Biochem 241:909–915
Burelle Y, Hochachka PW (2002) Endurance training induces muscle-specific changes in mitochondrial function in skinned muscle fibers. Appl Physiol 92:2429–2438
Phielix E, Meex R, Moonen-Kornips E et al (2010) Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals. Diabetologia 53:1714–1721
Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217:383–393
Seppet EK, Eimre M, Anmann T et al (2005) Intracellular energetic units in healthy and diseased hearts. Exp Clin Cardiol 10:173–183
Gellerich FN, Kapischke M, Kunz W et al (1994) The influence of the cytosolic oncotic pressure on the permeability of the mitochondrial outer membrane for ADP: implications for the kinetic properties of mitochondrial creatine kinase and for ADP channelling into the intermembrane space. Mol Cell Biochem 133/134:85–104
Gellerich FN, Laterveer FD, Korzeniewski B et al (1998) Dextrans strongly increase the Michaelis constants of oxidative phosphorylation and of mitochondrial creatine kinase in heart mitochondria. Eur J Biochem 254:172–180
Laterveer FD, Nicolay K, Gellerich FN (1997) Experimental evidences for dynamic compartmentation of ADP at mitochondrial periphery: coupling of mitochondrial adenylate kinase and mitochondrial hexokinase with oxidative phosphorylation under conditions mimicking the intracellular colloid osmotic pressure. Mol Cell Biochem 174:43–51
Saks V, Guzun R, Timohhina N et al (2010) Structure–function relationships in feedback regulation of energy fluxes in vivo in health and disease: mitochondrial interactosome. Biochim Biophys Acta 1797:678–697
Guerrero K, Monge C, Brückner A et al (2010) Study of possible interactions of tubulin, microtubular network, and STOP protein with mitochondria in muscle cells. Mol Cell Biochem 337:239–249
Walsh B, Tonkonogi M, Sahlin K (2001) Effect of endurance training on oxidative and antioxidative function in human permeabilized muscle fibres. Pflügers Arch 442:420–425
Zoll J, Sanchez H, N’Guessan B et al (2002) Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle. J Physiol 543:191–200
Stuewe SR, Gwirtz PA, Mallet RT (2001) Exercise training increases creatine kinase capacity in canine myocardium. Med Sci Sports 33:92–98
Apple FS, Rogers MA, Sherman WM et al (1984) Profile of creatine kinase isoenzymes in skeletal muscles of marathon runners. Clin Chem 30:413–416
Apple FE, Rogers MA (1986) Mitochondrial creatine kinase activity alterations in skeletal muscle during long-distance running. J Appl Physiol 61:482–485
Witteveen SA, Sobel BE, DeLuca M (1974) Kinetic properties of the isoenzymes of human creatine phosphokinase. Proc Natl Acad Sci U S A 71:1384–1387
Constable SH, Favier RJ, McLane JA et al (1987) Energy metabolism in contracting rat skeletal muscle: adaptation to exercise training. Am J Physiol 253:316–322
Gellerich FN, Gizatullina Z, Arandarcikaite O et al (2009) Extramitochondrial Ca2+ in the nanomolar range regulates glutamate-dependent oxidative phosphorylation on demand. PLoS One 4:28181
Gellerich FN, Gizatullina Z, Trumbeckaite S et al (2010) The regulation of OXPHOS by extramitochondrial calcium. Biochim Biophys Acta 1797:1018–1027
Gellerich FN, Gizatullina Z, Trumbekaite S et al (2012) Cytosolic Ca2+ regulates the oxidative phosphorylation of brain mitochondria via a metabolic pyruvate supply unit. Biochem J. doi:10.1042/BJ20110765
Papa S, Skulachev VP (1997) Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem 174:305–319
Brand MD (2010) The sites and topology of mitochondrial superoxide production. Exp Gerontol 45:466–472
Benani A, Troy S, Carmona MC et al (2007) Role for mitochondrial reactive oxygen species in brain lipid sensing: redox regulation of food intake. Diabetes 56:152–160
Hughes G, Murphy MP, Ledgerwood EC (2005) Mitochondrial reactive oxygen species regulate the temporal activation of nuclear factor κB to modulate tumour necrosis factor-induced apoptosis: evidence from mitochondria-targeted antioxidants. Biochem J 389:83–89
Lee S, Tak E, Lee J, Rashid MA et al (2011) Mitochondrial H2O2 generated from electron transport chain complex I stimulates muscle differentiation. Cell Res 21:817–834
Silva LA, Pinho CA, Scarabelot KS et al (2009) Physical exercise increases mitochondrial function and reduces oxidative damage in skeletal muscle. Eur J Appl Physiol 105:861–867
Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416:15–18
Malinska D, Kulawiak B, Kudin AP et al (2010) Complex III-dependent superoxide production of brain mitochondria contributes to seizure-related ROS formation. Biochim Biophys Acta 1797:1163–1170
Siu PM, Bryner RW, Martyn JK, Alway SE (2004) Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J 18:1150–1152
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
Powers SK, Quindry JC, Kavazis AN (2008) Exercise-induced cardioprotection against myocardial ischemia-reperfusion injury. Free Rad Biol Med 44:193–201
Lee SD, Shyu WC, Cheng IS, et al (2012) Effects of exercise training on cardiac apoptosis in obese rats. Nutr Metab Cardiovasc Dis (Mar 6). doi:10.1016/j.numecd.2011.11.002
Ascensão A, Lumini-Oliveira J, Machado NG et al (2011) Acute exercise protects against calcium-induced cardiac mitochondrial permeability transition pore opening in doxorubicin-treated rats. Clin Sci 120:37–49
Emter CA, Baines CP (2010) Low-intensity aerobic interval training attenuates pathological left ventricular remodelling and mitochondrial dysfunction in aortic-banded miniature swine. Am J Physiol Heart Circ Physiol 299:1348–1356
Chicco AJ, McCune SA, Emter CA et al (2008) Low-intensity exercise training delays heart failure and improves survival in female hypertensive heart failure rats. Hypertension 51:1096–1102
Kavazis AN, Alvarez S, Talbert E et al (2009) Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins. Am J Physiol 207:144–152
Kavazis AN, McClung JM, Hood DA, Powers SK (2008) Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli. Am J Physiol 294:928–935
Delchev SD, Georgieva KN, Koeva YA, Atanassova PK (2006) Bcl-2/Bax ratio, mitochondrial membranes and aerobic enzyme activity in cardiomyocytes of rats after submaximal training. Folia Med 48:50–56
French JP, Hamilton KL, Quindry JC et al (2008) Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASEB J 22:2862–2871
Hicks L, Fahimi HD (1977) Peroxisomes (microbodies) in the myocardium of rodents and primates. A comparative ultrastructural cytochemical study. Cell Tissue Res 175:467–481
Kreider R, Fry AC, O’Toole M (1998) Overtraining in sports: terms, definitions, and prevalence. In: Kreider R, Fry AC, O’Toole M (eds) Overtraining in sport. Human Kinetics, Champaign, IL, pp 47–66
Seene T, Umnova M, Kaasik P (1999) The exercise myopathy. In: Lehman M et al (eds) Overload, perfomance incompetence, and regeneration in sport. Kluwer Academic Plenum Publisher, New York, pp 119–130
Seene T, Kaasik P, Alev K et al (2004) Composition and turnover of contractile proteins in volume-overtrained skeletal muscle. Int J Sports Med 25:438–445
Seene T, Kaasik P, Umnova M (2009) Structural rearrangements in contractile apparatus and resulting skeletal muscle remodelling: effect of exercise training. J Sports Med Phys Fitness 49:410–423
Kadaja L, Eimre M, Paju K et al (2010) Impaired oxidative phosphorylation in overtrained rat myocardium. Exp Clin Cardiol 15:116–127
Dirks A, Leeuwenburgh C (2005) The role of apoptosis in age-related skeletal muscle atrophy. Sports Med 35:473–483
Abbiss CR, Laursen PB (2005) Models to explain fatigue during prolonged endurance cycling. Sports Med 35:865–898
King DW, Gollnick PD (1970) Ultrastructure of rat heart and liver after exhaustive exercise. Am J Physiol 218:1150–1155
Coleman R, Silbermann M, Gershon D, Reznick AZ (1987) Giant mitochondria in the myocardium of aging and endurance-trained mice. Gerontology 33:34–39
Taylor PB, Lamb DR, Budd GC (1976) Structure and function of cardiac mitochondria in exhausted guinea pigs. Eur J Appl Physiol Occup Physiol 35:111–118
Ding H, Jiang N, Liu H et al (1800) Response of mitochondrial fusion and fission protein gene expression to exercise in rat skeletal muscle. Biochim Biophys Acta 250–256:2010
Brancaccio P, Maffulli N, Limongelli FM (2007) Creatine kinase monitoring in sport medicine. Br Med Bull 81–82:209–230
Bronheimer JF, Lau F (1981) Effects of treadmill exercise on total and myocardial creatine phosphokinase. Chest 80:146–148
Jaffe AS, Garfinkel BT, Ritter CS, Sobel BE (1984) Plasma MB creatine kinase after vigorous exercise in professional athletes. Am J Cardiol 53:856–858
Young A (1984) Plasma creatine kinase after the marathon—a diagnostic dilemma. Brit J Sports Med 18:269–272
Apple FS, Billadello JJ (1994) Expression of creatine kinase M and B mRNAs in treadmill trained rat skeletal muscle. Life Sci 55:585–592
Cummins P, Young A, Auckland ML et al (1987) Comparison of serum cardiac specific troponin-I with creatine kinase, creatine kinase-MB isoenzyme, tropomyosin, myoglobin and C-reactive protein release in marathon runners: cardiac or skeletal muscle trauma? Eur J Clin Invest 17:317–324
Siegel AJ, Sholar M, Yang J et al (1997) Elevated serum cardiac markers in asymptomatic marathon runners after competition: is the myocardium stunned? Cardiology 88:487–491
Nie J, Tong TK, George K et al (2011) Resting and post-exercise serum biomarkers of cardiac and skeletal muscle damage in adolescent runners. Scand J Med Sci Sports 21:625–629
Nanji AA (1983) Serum creatine kinase isoenzymes: a review. Muscle Nerve 6:83–90
Chen YJ, Serfass RC, Apple FS (2000) Loss of myocardial CK-MB into the circulation following 3.5 hours of swimming in a rat model. Int J Sports Med 21:561–565
Miller TD, Rogers PJ, Bauer BA et al (1989) Does exercise training alter myocardial creatine kinase MB isoenzyme content? Med Sci Sports Exerc 21:437–440
Kainulainen H, Ahomäki E, Vihko V (1984) Selected enzyme activities in mouse cardiac muscle during training and terminated training. Basic Res Cardiol 79:110–123
Pan SS (2008) Alterations of atrial natriuretic peptide in cardiomyocytes and plasma of rats after different intensity exercise. Scan J Med Sci Sports 18:346–353
Margonis K, Fatouros IG, Jamurtas AZ et al (2007) Oxidative stress biomarkers responses to physical overtraining: implications for diagnosis. Free Rad Biol Med 43:901–910
Acknowledgments
This study was supported by the grants from Estonian Science Foundation No 7117, 7823, and 8736 and by a grant SF0180114As08 from Estonian Ministry of Education and Research.
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Seppet, E., Orlova, E., Seene, T., Gellerich, F.N. (2013). Adaptation of Cardiac and Skeletal Muscle Mitochondria to Endurance Training: Implications for Cardiac Protection. In: Ostadal, B., Dhalla, N. (eds) Cardiac Adaptations. Advances in Biochemistry in Health and Disease, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5203-4_20
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