Subscribe to RSS
DOI: 10.1055/s-2005-837570
© Georg Thieme Verlag KG Stuttgart · New York
Cardiac Mitochondrial Respiratory Function and Oxidative Stress: The Role of Exercise
Publication History
Accepted after revision: January 10, 2005
Publication Date:
29 March 2005 (online)
Abstract
Investigations on the mechanisms capable of influencing heart mitochondrial function constitute a central contribution to the understanding of cardiac bioenergetics. In contrast to the conventional idea that reactive oxygen species (ROS) mostly act as a trigger for oxidative damage of biological structures, in low physiological concentrations they can regulate a variety of important molecular mechanisms, including those related to mitochondrial respiratory function. Among others, moderate physical exercise seems to be an important agent to induce cellular and mitochondrial environmental redox modifications and it is possible that these alterations could mediate cardiac mitochondrial respiration patterns. This brief review summarizes some current knowledge on mitochondrial respiratory pathways and focuses on data provided by studies dealing with exercise and cardiac respiratory mechanisms. It is emphasized the need of further experimental studies that analyze the association between physical exercise, particularly endurance training, and several mechanisms hypothetically related to the improvement of mitochondrial function, such as the overexpression of some important chaperone machinery and the up-regulation of both cellular and mitochondrial antioxidants. The influence of chronic moderate exercise on the functionality of some inner membrane components and on mitochondrial calcium loading capacity remains to be established.
Key words
Respiration - oxygen consumption - heart - training - reactive oxygen species
References
- 1 Ascensao A, Magalhaes J, Soares J, Oliveira J, Duarte J A. Exercise and cardiac oxidative stress. Rev Port Cardiol. 2003; 22 651-678
- 2 Asha Devi S, Prathima S, Subramanyam M V. Dietary vitamin E and physical exercise: II. Antioxidant status and lipofuscin-like substances in aging rat heart. Exp Gerontol. 2003; 38 291-297
- 3 Atalay M, Sen C K. Physical exercise and antioxidant defenses in the heart. Ann NY Acad Sci. 1999; 874 169-177
- 4 Becker L B, vanden Hoek T L, Shao Z H, Li C Q, Schumacker P T. Generation of superoxide in cardiomyocytes during ischemia before reperfusion. Am J Physiol. 1999; 277 H2240-2246
- 5 Boss O, Samec S, Desplanches D, Mayet M H, Seydoux J, Muzzin P, Giacobino J P. Effect of endurance training on mRNA expression of uncoupling proteins 1, 2, and 3 in the rat. Faseb J. 1998; 12 335-339
- 6 Chakraborti T, Das S, Mondal M, Roychoudhury S, Chakraborti S. Oxidant, mitochondria and calcium: an overview. Cell Signal. 1999; 11 77-85
- 7 Chance B, Williams G R. The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem. 1956; 17 65-134
- 8 Chen Q, Vazquez E J, Moghaddas S, Hoppel C L, Lesnefsky E J. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem. 2003; 278 36027-36031
- 9 Chernyak B V. Redox regulation of the mitochondrial permeability transition pore. Biosci Rep. 1997; 17 293-302
- 10 Colucci W S. Molecular and cellular mechanisms of myocardial failure. Am J Cardiol. 1997; 80 15L-25L
- 11 Crompton M. Mitochondria and aging: a role for the permeability transition?. Aging Cell. 2004; 3 3-6
- 12 Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999; 341 233-249
- 13 Davies K J, Doroshow J H. Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J Biol Chem. 1986; 261 3060-3067
- 14 Dhalla N S, Elmoselhi A B, Hata T, Makino N. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res. 2000; 47 446-456
- 15 Di Meo S, Venditti P. Mitochondria in exercise-induced oxidative stress. Biol Signals Recept. 2001; 10 125-140
- 16 Diehl A M, Hoek J B. Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control “the benefits of losing control”. J Bioenerg Biomembr. 1999; 31 493-506
- 17 Du G, Mouithys-Mickalad A, Sluse F E. Generation of superoxide anion by mitochondria and impairment of their functions during anoxia and reoxygenation in vitro. Free Radic Biol Med. 1998; 25 1066-1074
- 18 Fernstrom M, Tonkonogi M, Sahlin K. Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle. J Physiol. 2004; 554 755-763
- 19 Ferranti R, da Silva M M, Kowaltowski A J. Mitochondrial ATP-sensitive K+ channel opening decreases reactive oxygen species generation. FEBS Lett. 2003; 536 51-55
- 20 Giacobino J P. Uncoupling protein 3 biological activity. Biochem Soc Trans. 2001; 29 774-777
- 21 Halliwell B, Gutteridge J M. Free Radicals in Biology and Medicine. Oxford; Clarendon Press 1999
- 22 Hamilton K L, Staib J L, Phillips T, Hess A, Lennon S L, Powers S K. Exercise, antioxidants, and HSP72: protection against myocardial ischemia/reperfusion. Free Radic Biol Med. 2003; 34 800-809
- 23 Hengartner M O. The biochemistry of apoptosis. Nature. 2000; 407 770-776
- 24 Hesselink M K, Schrauwen P, Holloszy J O, Jones T E. Divergent effects of acute exercise and endurance training on UCP3 expression. Am J Physiol Endocrinol Metab. 2003; 284 E449-450 450-451 (author reply)
- 25 Hirsch T, Marzo I, Kroemer G. Role of the mitochondrial permeability transition pore in apoptosis. Biosci Rep. 1997; 17 67-76
- 26 Hoffmann B, Stockl A, Schlame M, Beyer K, Klingenberg M. The reconstituted ADP/ATP carrier activity has an absolute requirement for cardiolipin as shown in cysteine mutants. J Biol Chem. 1994; 269 1940-1944
-
27 Hood D, Rungi A, Colavecchia M, Gordon J, Schneider J.
Stress proteins and mitochondria. Locke M, Noble E Exercise and Stress Response - the Role of Stress Proteins. Boca Raton, Florida; CRC Press 2002: 151-162 - 28 Hood D A, Adhihetty P J, Colavecchia M, Gordon J W, Irrcher I, Joseph A M, Lowe S T, Rungi A A. Mitochondrial biogenesis and the role of the protein import pathway. Med Sci Sports Exerc. 2003; 35 86-94
- 29 Hood D A, Balaban A, Connor M K, Craig E E, Nishio M L, Rezvani M, Takahashi M. Mitochondrial biogenesis in striated muscle. Can J Appl Physiol. 1994; 19 12-48
- 30 Ide T, Tsutsui H, Kinugawa S, Utsumi H, Kang D, Hattori N, Uchida K, Arimura K, Egashira K, Takeshita A. Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium. Circ Res. 1999; 85 357-363
- 31 Irrcher I, Adhihetty P J, Joseph A M, Ljubicic V, Hood D A. Regulation of mitochondrial biogenesis in muscle by endurance exercise. Sports Med. 2003; 33 783-793
-
32 Ji L.
Exercise-induced oxidative stress in the heart. Sen CK, Packer L, Hanninen O Handbook of Oxidants and Antioxidants in Exercise. Basel; Elsevier Science B. V. 2000: 689-712 - 33 Ji L L. Antioxidants and oxidative stress in exercise. Proc Soc Exp Biol Med. 1999; 222 283-292
- 34 Ji L L. Exercise and oxidative stress: role of the cellular antioxidant systems. Exerc Sport Sci Rev. 1995; 23 135-166
- 35 Ji L L. Exercise-induced modulation of antioxidant defense. Ann NY Acad Sci. 2002; 959 82-92
- 36 Ji L L, Mitchell E W. Effects of Adriamycin on heart mitochondrial function in rested and exercised rats. Biochem Pharmacol. 1994; 47 877-885
- 37 Jones T E, Baar K, Ojuka E, Chen M, Holloszy J O. Exercise induces an increase in muscle UCP3 as a component of the increase in mitochondrial biogenesis. Am J Physiol Endocrinol Metab. 2003; 284 E96-101
-
38 Kappus H.
Lipid Peroxidation: mechanisms, analysis, enzymology and biological relevance. Sies H Oxidative Stress. London; Academic Press Inc 1985: 273-310 - 39 Kokoszka J E, Waymire K G, Levy S E, Sligh J E, Cai J, Jones D P, MacGregor G R, Wallace D C. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature. 2004; 427 461-465
- 40 Korshunov S S, Korkina O V, Ruuge E K, Skulachev V P, Starkov A A. Fatty acids as natural uncouplers preventing generation of O2 •- and H2O2 by mitochondria in the resting state. FEBS Lett. 1998; 435 215-218
- 41 Korshunov S S, Skulachev V P, Starkov A A. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett. 1997; 416 15-18
- 42 Kowaltowski A J, Castilho R F, Vercesi A E. Mitochondrial permeability transition and oxidative stress. FEBS Lett. 2001; 495 12-15
- 43 Kroemer G, Dallaporta B, Resche-Rigon M. The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol. 1998; 60 619-642
- 44 Lefer D J, Granger D N. Oxidative stress and cardiac disease. Am J Med. 2000; 109 315-323
- 45 Leichtweis S B, Leeuwenburgh C, Parmelee D J, Fiebig R, Ji L L. Rigorous swim training impairs mitochondrial function in post-ischaemic rat heart. Acta Physiol Scand. 1997; 160 139-148
- 46 Miwa S, Brand M D. Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling. Biochem Soc Trans. 2003; 31 1300-1301
- 47 Monteiro P, Oliveira P J, Goncalves L, Providencia L A. Mitochondria: role in ischemia, reperfusion and cell death. Rev Port Cardiol. 2003; 22 233-254
- 48 Ozcan C, Bienengraeber M, Dzeja P P, Terzic A. Potassium channel openers protect cardiac mitochondria by attenuating oxidant stress at reoxygenation. Am J Physiol Heart Circ Physiol. 2002; 282 H531-539
- 49 Paffenbarger Jr R S, Hyde R T, Wing A L, Hsieh C C. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med. 1986; 314 605-613
- 50 Paradies G, Petrosillo G, Pistolese M, Di Venosa N, Serena D, Ruggiero F M. Lipid peroxidation and alterations to oxidative metabolism in mitochondria isolated from rat heart subjected to ischemia and reperfusion. Free Radic Biol Med. 1999; 27 42-50
- 51 Perez A C, Cabral de Oliveira A C, Estevez E, Molina A J, Prieto J G, Alvarez A I. Mitochondrial, sarcoplasmic membrane integrity and protein degradation in heart and skeletal muscle in exercised rats. Comp Biochem Physiol C Toxicol Pharmacol. 2003; 134 199-206
- 52 Phaneuf S, Leeuwenburgh C. Apoptosis and exercise. Med Sci Sports Exerc. 2001; 33 393-396
- 53 Powers S K, Demirel H A, Vincent H K, Coombes J S, Naito H, Hamilton K L, Shanely R A, Jessup J. Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. Am J Physiol. 1998; 275 R1468-1477
- 54 Primeau A J, Adhihetty P J, Hood D A. Apoptosis in heart and skeletal muscle. Can J Appl Physiol. 2002; 27 349-395
- 55 Ricquier D, Bouillaud F. Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance. J Physiol. 2000; 529 3-10
- 56 Samelman T R. Heat shock protein expression is increased in cardiac and skeletal muscles of Fischer 344 rats after endurance training. Experimental Physiology. 2000; 85 97-102
- 57 Sammut I A, Harrison J C. Cardiac mitochondrial complex activity is enhanced by heat shock proteins. Clin Exp Pharmacol Physiol. 2003; 30 110-115
- 58 Sammut I A, Jayakumar J, Latif N, Rothery S, Severs N J, Smolenski R T, Bates T E, Yacoub M H. Heat stress contributes to the enhancement of cardiac mitochondrial complex activity. Am J Pathol. 2001; 158 1821-1831
- 59 Santos D L, Moreno A J, Leino R L, Froberg M K, Wallace K B. Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy. Toxicol Appl Pharmacol. 2002; 185 218-227
- 60 Sen C K. Antioxidant and redox regulation of cellular signaling: introduction. Med Sci Sports Exerc. 2001; 33 368-370
-
61 Sen C K, Goldfarb A.
Antioxidants and physical exercise. Sen CK, Packer L, Hanninen O Handbook of Oxidants and Antioxidants in Exercise. Basel; Elsevier Science B. V. 2000: 297-320 - 62 Shern-Brewer R, Santanam N, Wetzstein C, White-Welkley J, Parthasarathy S. Exercise and cardiovascular disease: a new perspective. Arterioscler Thromb Vasc Biol. 1998; 18 1181-1187
- 63 Simonyan R A, Skulachev V P. Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein. FEBS Lett. 1998; 436 81-84
- 64 Skulachev V P. Cytochrome C in the apoptotic and antioxidant cascades. FEBS Lett. 1998; 423 275-280
- 65 Skulachev V P. Membrane-linked systems preventing superoxide formation. Biosci Rep. 1997; 17 347-366
- 66 Smaili S S, Hsu Y T, Carvalho A C, Rosenstock T R, Sharpe J C, Youle R J. Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling. Braz J Med Biol Res. 2003; 36 183-190
- 67 Suzuki K, Murtuza B, Sammut I A, Latif N, Jayakumar J, Smolenski R T, Kaneda Y, Sawa Y, Matsuda H, Yacoub M H. Heat shock protein 72 enhances manganese superoxide dismutase activity during myocardial ischemia-reperfusion injury, associated with mitochondrial protection and apoptosis reduction. Circulation. 2002; 106 I 270-276
- 68 Tiidus P M, Houston M E. Vitamin E status and response to exercise training. Sports Med. 1995; 20 12-23
-
69 Tirosh O, Reznick A.
Chemical bases and biological relevance of protein oxidation. Sen CK, Packer L, Hanninen O Handbook of Oxidants and Antioxidants in Exercise. Basel; Elsevier Science B. V. 2000: 89-114 - 70 Tonkonogi M, Krook A, Walsh B, Sahlin K. Endurance training increases stimulation of uncoupling of skeletal muscle mitochondria in humans by non-esterified fatty acids: an uncoupling-protein-mediated effect?. Biochem J. 2000; 351 805-810
- 71 Tonkonogi M, Sahlin K. Physical exercise and mitochondrial function in human skeletal muscle. Exerc Sport Sci Rev. 2002; 30 129-137
- 72 Tonkonogi M, Walsh B, Svensson M, Sahlin K. Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress. J Physiol. 2000; 528 379-388
- 73 Venditti P, Di Meo S. Antioxidants, tissue damage, and endurance in trained and untrained young male rats. Arch Biochem Biophys. 1996; 331 63-68
- 74 Vercesi A E, Kowaltowski A J, Grijalba M T, Meinicke A R, Castilho R F. The role of reactive oxygen species in mitochondrial permeability transition. Biosci Rep. 1997; 17 43-52
- 75 Voos W, Rottgers K. Molecular chaperones as essential mediators of mitochondrial biogenesis. Biochim Biophys Acta. 2002; 1592 51-62
- 76 Wallace K B. Doxorubicin-induced cardiac mitochondrionopathy. Pharmacol Toxicol. 2003; 93 105-115
- 77 Wallace K B, Eells J T, Madeira V M, Cortopassi G, Jones D P. Mitochondria-mediated cell injury. Symposium overview. Fundam Appl Toxicol. 1997; 38 23-37
António Ascensão
Department of Sport Biology
Faculty of Sport Sciences, University of Porto
Rua Dr. Plácido Costa, 91
4200-450 Porto
Portugal
Phone: + 351225074774
Fax: + 35 12 25 50 06 89
Email: aascensao@fcdef.up.pt