Role of Antioxidant Signaling in Mitochondrial Adaptation to Muscle Contraction

  • Li Li Ji
Reference work entry


Generation of reactive oxygen species (ROS) is a ubiquitous biological phenomenon in eukaryotic cell life. It has become clear that ROS at the physiological concentration are not merely damaging agents inflicting random destruction to the cell structure and function but useful signaling molecules to regulate a wide range of physiological functions such as metabolism, antioxidant defense, organ remodeling, and aging (Hawley and Zierath 2004; D’Autréaux and Toledano 2007; Pourova et al. 2010; Collins et al. 2012). Understanding how the cell controls the level of ROS production and regulates the signal transduction process is essential for us to develop strategies in order to prevent diseases and improve cell functionality. In healthy people, muscle contraction-induced generation of ROS represents a major portion of all the ROS produced in the body and can stimulate a host of events that modulate energy metabolism, oxidative-antioxidant homeostasis, cellular structural changes (such as mitochondrial biogenesis, fiver hypertrophy), and even muscle force production. The majority of these adaptations require de novo protein synthesis through transcription, translation, and protein transport. These cellular events have been termed “signal transduction” or simply “signaling.” It is noteworthy that signaling pathways do not operate separately but often interact with each other to process and transfer signals, termed “cross talk,” that involves multiple organelles and cellular compartments. Mitochondria as the main organelle that generate the balk of ROS and tightly regulate ROS removal and release maintain a stable ROS output mainly in form of H2O2, but also in other forms such as NO. Mitochondria also participate in the regulation of its proliferation and remodeling mainly through the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1) family transcriptional cofactors (Handschin and Spiegelman 2008). This chapter will briefly describe the mechanism, gene targets and functions of several most important cell signaling pathways, and the role of mitochondria in such regulation. In this chapter, skeletal muscle is the main focus of discussion because of its high plasticity and a wide range of adaptations demonstrated in response to increased metabolic demand and stress. The role of muscle contraction will be highlighted throughout the discussions. For basic antioxidant signaling mechanisms, the readers are referred to an abundant volume of review articles published during the past decade; some of them will be selectively quoted whenever applicable.


Reactive Oxygen Species Reactive Oxygen Species Production Mitochondrial Biogenesis Redox Signaling Mitochondrial Fission 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adams V, Nehrhoff B, Spate U, Linke A, Schulze PC, Baur A, Gielen S, Hambrecht R, Schuler G (2002) Induction of iNOS expression in skeletal muscle by IL-1beta and NFkappaB activation: an in vitro and in vivo study. J Cardiovasc Res 54(1):95–104Google Scholar
  2. Akimoto T, Pohnert SC, Li P, Zhang M, Gumbs C, Rosenberg PB, Williams RS, Yan Z (2005) Exercise stimulates Pgc-1α transcription in skeletal muscle through activation of the p38 MAPK pathway. J Biol Chem 280:19587–19593PubMedGoogle Scholar
  3. Allen RG, Tresini M (2000) Oxidative stress and gene regulation. J Free Radic Biol Med 28:463–499Google Scholar
  4. Anderson EJ, Yamazaki H, Neufer PD (2007) Induction of endogenous uncoupling protein 3 suppresses mitochondrial oxidant emission during fatty acid-supported respiration. J Biol Chem 282:31257–31266PubMedGoogle Scholar
  5. Aon MA, Cortassa S, O’Rourke B (2010) Redox-optimized ROS balance: a unifying hypothesis. Biochim Biophys Acta 1797(6–7):865–877PubMedCentralPubMedGoogle Scholar
  6. Arnold AS, Egger A, Handschin C (2010) PGC-1α and myokines in the aging muscle—a mini-review. J Gerontol 57:37–43Google Scholar
  7. Baar K, Esser K (1999) Phosphorylation of P70S6K correlates with increased skeletal muscle mass following resistance exercise. Am J Physiol Cell Physiol 276:C120–C127Google Scholar
  8. Baar K, Wende AR, Jones TE, Marison M, Nolte LA, Chen M, Kelly DP, Holloszy JO (2002) Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J 16:1879–1886PubMedGoogle Scholar
  9. Bach D, Pich S, Soriano FX, Vega N, Baumgartner B, Oriola J, Daugaard JR, Lloberas J, Camps M, Zierath JR, Rabasa-Lhoret R, Wallberg-Henriksson H, Laville M, Palacin M, Vidal H, Rivera F, Brand M, Zorzano A (2003) Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem 278:17190–17197PubMedGoogle Scholar
  10. Balon TW (1999) Integrative biology of nitric oxide and exercise. J Exerc Sport Sci Rev 27:219–253Google Scholar
  11. Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, De Benedictis G (2005) A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. J Genomics 85:258–263Google Scholar
  12. Bergelson S, Pinkus R, Daniel V (1994) Induction of AP-1 (Fos/Jun) by chemical agents mediates activation of glutathione S-transferase and quinone reductase gene expression. J Oncogene 9:565–571Google Scholar
  13. 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 Radic Biol Med 44(7):1373–1381PubMedGoogle Scholar
  14. Bo H, Zhang Y, Ji LL (2010) Redefining the role of mitochondria in exercise: a dynamic remodeling. J Ann N Y Acad Sci 1201:121–128Google Scholar
  15. Breckenridge DG, Kang BH, Kokel D, Mitani S, Staehelin LA, Xue D (2008) Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9. J Mol Cell 31:586–597Google Scholar
  16. Burge WE, Neil AJ (1916–17) Comparison of the amount of catalase in the muscle of large and of small animals. Am J Physiol 43:433–437Google Scholar
  17. Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S (2004) p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. J Mol Cell Biol 24:3057–3067Google Scholar
  18. Cartoni R, Léger B, Hock MB, Praz M, Crettenand A, Pich S, Ziltener JL, Luthi F, Dériaz O, Zorzano A, Gobelet C, Kralli A, Russell AP (2005) Mitofusins 1/2 and ERR alpha expression are increased in human skeletal muscle after physical exercise. J Physiol 567:349–358PubMedCentralPubMedGoogle Scholar
  19. Catani MV, Savini I, Duranti G, Caporossi D, Ceci R, Sabatini S, Avigliano L (2004) Nuclear factor kappaB and activating protein 1 are involved in differentiation-related resistance to oxidative stress in skeletal muscle cells. J Free Radic Biol Med 37:1024–1036Google Scholar
  20. Chan JY, Kwong M (2000) Impaired expression of glutathione synthetic enzyme genes in mice with targeted deletion of the Nrf2 basic-leucine zipper protein. J Biochim Biophys Acta 1517:19–26Google Scholar
  21. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. J Physiol Rev 59:527–605Google Scholar
  22. Collins Y, Chouchani ET, James AM, Menger KE, Cochemé HM, Murphy MP (2012) Mitochondrial redox signalling at a glance. J Cell Sci 125(Pt 4):801–806PubMedGoogle Scholar
  23. Cortright RN, Zheng D, Jones JP, Fluckey JD, DiCarlo SE, Grujic D, Lowell BB, Dohm GL (1999) Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation. Am J Physiol Endocrinol Metab 276:E217–E221Google Scholar
  24. Cox AG, Winterbourn CC, Hampton MB (2009) Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signaling. Biochem J 425(2):313–325PubMedGoogle Scholar
  25. D’Autréaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824PubMedGoogle Scholar
  26. Ding H, Jiang N, Liu H, Liu X, Liu D, Zhao F, Wen L, Liu S, Ji LL, Zhang Y (2009) Response of mitochondrial fusion and fission protein gene expression to exercise in rat skeletal muscle. J Biochim Biophys Acta 1800:250–256Google Scholar
  27. Feng H, Kang C, Dickman J et al (2013) Training-induced mitochondrial adaptation: role of PGC-1á, NFêB and â-blockade. Exp Physiol. 98(3):784–795PubMedGoogle Scholar
  28. Finck BN, Kelly DP (2006) PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116:615–622PubMedCentralPubMedGoogle Scholar
  29. Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194(1):7–15PubMedCentralPubMedGoogle Scholar
  30. Flohé L, Brigelius-Flohé R, Saliou C, Traber M, Packer L (1997) Redox regulation of NF-kappa B activation. J Free Radic Biol Med 22:1115–1126Google Scholar
  31. Garnier A, Fortin D, Zoll J, N’Guessan B, Mettauer B, Lampert E, Veksler V, Ventura-Clapier R (2005) Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle. FASEB J 19:43–52PubMedGoogle Scholar
  32. Geng T, Li P, Okutsu M (2010) PGC-1α plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. Am J Physiol Cell Physiol 298:572–579Google Scholar
  33. Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. J Cell 109(Suppl):S81–S96Google Scholar
  34. Goglia F, Skulachev VP (2003) A function for novel uncoupling proteins: antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet. FASEB J 17:1585–1591PubMedGoogle Scholar
  35. Gomes LC, Scorrano L (2008) High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim Biophys Acta 1777:860–866PubMedGoogle Scholar
  36. Gomez-Cabrera MC, Borras C, Pallardó FV, Sastre J, Ji LL, Vina J (2005) Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats. J Physiol 567:113–120PubMedCentralPubMedGoogle Scholar
  37. Goodyear L, Chang P, Sherwood D, Dufresne S, Moller D (1996) Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle. Am J Physiol 271:E403–E408PubMedGoogle Scholar
  38. Grandemange S, Herzig S, Martinou JC (2009) Mitochondrial dynamics and cancer. J Semin Cancer Biol 19:50–56Google Scholar
  39. Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35(9):505–513PubMedCentralPubMedGoogle Scholar
  40. Handschin C (2009) Peroxisome proliferator-activated receptor-γ coactivator-1α in muscle links metabolism to inflammation. J Clin Exp Pharmacol Physiol 36:1139–1143Google Scholar
  41. Handschin C (2010) Regulation of skeletal muscle cell plasticity by the peroxisome proliferator-activated receptor γ coactivator 1α. J Recept Signal Transduct 30:376–384Google Scholar
  42. Handschin C, Spiegelman BM (2008) The role of exercise and PGC1α in inflammation and chronic disease. J Nature 454:463–469Google Scholar
  43. Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, Spiegelman BM (2007) Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals. J Biol Chem 282:30014–30021PubMedGoogle Scholar
  44. Hawley JA, Zierath JR (2004) Integration of metabolic and mitogenic signal transduction in skeletal muscle. J Exerc Sport Sci Rev 32:4–8Google Scholar
  45. Hoffmann E, Thiefes A, Buhrow D, Dittrich-Breiholz O, Schneider H, Resch K, Kracht M (2005) MEK1-dependent delayed expression of Fos-related antigen-1 counteracts c-Fos and p65 NF-kappaB-mediated interleukin-8 transcription in response to cytokines or growth factors. J Biol Chem 280:9706–9718PubMedGoogle Scholar
  46. Hollander J, Fiebig R, Ookawara T, Ohno H, Ji LL (2001) Superoxide dismutase gene expression is activated by a single bout of exercise in rat skeletal muscle. Pflug Arch Eur J Physiol 442(3):426–434Google Scholar
  47. Holloszy JO (1967) Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem 242:2278–2282PubMedGoogle Scholar
  48. Holloszy JO, Coyle EF (1984) Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56:831–838PubMedGoogle Scholar
  49. Hom J, Sheu SS (2009) Morphological dynamics of mitochondria – a special emphasis on cardiac muscle cells. J Mol Cell Cardiol 46:811–820PubMedCentralPubMedGoogle Scholar
  50. Irrcher I, Adhihetty PJ, Sheehan T, Joseph AM, Hood DA (2003) PPARgamma coactivator-1alpha expression during thyroid hormone- and contractile activity-induced mitochondrial adaptations. Am J Physiol Cell Physiol 284:1669–1677Google Scholar
  51. Jagoe RT, Goldberg AL (2001) What do we really know about the ubiquitin – proteasome pathway in muscle atrophy? J Curr Opin Clin Nutr Metab Care 4:183–190Google Scholar
  52. Jendrach M, Mai S, Pohl S, Voth M, Bereiter-Hahn J (2008) Short- and long-term alterations of mitochondrial morphology, dynamics and mtDNA after transient oxidative stress. J Mitochondrion 8:293–304Google Scholar
  53. Jenkins RR (1993) Exercise, oxidative stress and antioxidant: a review. Intl J Sport Nutr 3:356–375Google Scholar
  54. Ji LL (1995) Exercise and oxidative stress: role of the cellular antioxidant systems. J Exerc Sport Sci Rev 23:135–166Google Scholar
  55. Ji LL (2007) Antioxidant signaling in skeletal muscle: a brief review. J Exp Gerontol 42(7):582–593Google Scholar
  56. Ji LL, Fu RG, Mitchell EW (1992) Glutathione and antioxidant enzymes in skeletal muscle: effects of fiber type and exercise intensity. J Appl Physiol 73:1854–1859PubMedGoogle Scholar
  57. Ji LL, Gomez-Cabrera MC, Steinhafel N, Vina J (2004) Acute exercise activates nuclear factor (NF) κB signaling pathway in rat skeletal muscle. FASEB J 18:1499–1506PubMedGoogle Scholar
  58. Jiang B, Xu S, Hou X, Pimentel DR, Brecher P, Cohen RA (2004) Temporal control of NF-kappaB activation by ERK differentially regulates interleukin-1beta-induced gene expression. J Biol Chem 279:1323–1329PubMedGoogle Scholar
  59. Jiang N, Zhang G, Bo H et al (2009) Upregulation of uncoupling protein-3 in skeletal muscle during exercise: a potential antioxidant function. Free Radic Biol Med 46(2):138–145PubMedGoogle Scholar
  60. 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 47:1394–1400PubMedGoogle Scholar
  61. Karbowski M, Neutzner A, Youle RJ (2007) The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. J Cell Biol 178:71–84PubMedCentralPubMedGoogle Scholar
  62. Kelly DP, Scarpulla RC (2007) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. J Genes Dev 18:357–368Google Scholar
  63. Klingenberg M, Huang SG (1999) Structure and function of the uncoupling protein from brown adipose tissue. Biochim Biophys Acta 1415:271–296PubMedGoogle Scholar
  64. Knutti D, Kralli A (2001) PGC-1, a versatile coactivator. Trends Endocrinol Metab 12:360–365PubMedGoogle Scholar
  65. Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, Fang F, Chang Y (2010) Sirtuin 3, a new target of PGC-1α, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One 5:e11707PubMedCentralPubMedGoogle Scholar
  66. Koopman WJ, Verkaart S, van Emst-de Vries SE, Grefte S, Smeitink JA, Nijtmans LG, Willems PH (2008) Mitigation of NADH: ubiquinone oxidoreductase deficiency by chronic Trolox treatment. Biochim Biophys Acta 1777:853–859PubMedGoogle Scholar
  67. Krauss S, Zhang CY, Lowell BB (2005) The mitochondrial uncoupling-protein homologues. Nat Rev Mol Cell Biol 6:248–261PubMedGoogle Scholar
  68. Kuznetsov AV, Hermann M, Saks V, Hengster P, Margreiter R (2009) The cell-type specificity of mitochondrial dynamics. Int J Biochem Cell Biol 41(10):1928–1939PubMedGoogle Scholar
  69. Leick L, Wojtaszewski JF, Johansen ST (2008) PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol 294:463–474Google Scholar
  70. Leick L, Lyngby SS, Wojtasewski JF, Pilegaard H (2010) PGC-1α is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle. Exp Gerontol 45:336–342PubMedGoogle Scholar
  71. Li Q, Engelhardt JF (2006) Interlecukin-1β induction of NFκB is partially regulated by H2O2-mediated activation of NFκB-inducing kinase. J Biol Chem 281:1495–1505PubMedGoogle Scholar
  72. Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA, Orth A, Chanda SK, Batalov S, Joazeiro CA (2008) Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle’s dynamics and signaling. PLoS One 3:e1487PubMedCentralPubMedGoogle Scholar
  73. Liesa M, Borda-d AB, Medina-Gomez G, Lelliott CJ, Paz JC, Rojo M, Palacin M, Vidal-Puig A, Zorzano A (2008) Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta. PLoS One 3:e3613PubMedCentralPubMedGoogle Scholar
  74. Liesa M, Palacin M, Zorzano A (2009) Mitochondrial dynamics in mammalian health and disease. Physiol Rev 89:799–845PubMedGoogle Scholar
  75. Lin J, Wu H, Tarr PT (2002) Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. Nature 418:797–801PubMedGoogle Scholar
  76. Lin J, Handschin C, Spiegelman BM (2005) Metabolic control through the PGC-1 family of transcription coactivators. J Cell Metabol 1:361–370Google Scholar
  77. Ljubicic V, Adhihetty PJ, Hood DA (2004) Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis. J Appl Physiol 97:976–983PubMedGoogle Scholar
  78. Long YC, Widegren U, Zierath JR (2004) Exercise-induced mitogen-activated protein kinase signalling in skeletal muscle. J Proc Nutr Soc 63:227–232Google Scholar
  79. Manoli I, Alesci S, Blackman MR, Su YA, Rennert OM, Chrousos GP (2007) Mitochondria as key components of the stress response. Trends Endocrinol Metab 18(5):190–198PubMedGoogle Scholar
  80. Meyer M, Pahl HL, Baeuerle PA (1994) Regulation of the transcription factors NF-kB and AP-1 by redox changes. J Chem Biol Interact 91:91–100Google Scholar
  81. Michael LF, Wu Z, Cheatham RB (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci USA 98:3820–3825PubMedCentralPubMedGoogle Scholar
  82. Monteiro HP, Stern A (1996) Redox modulation of tyrosine phosphorylation-dependent signal transduction pathways. Free Radic Biol Med 21:323–333PubMedGoogle Scholar
  83. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC (2003) PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. J Nat Genet 34:267–273Google Scholar
  84. Nakamura N, Kimura Y, Tokuda M, Honda S, Hirose S (2006) MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO Rep 7:1019–1022PubMedCentralPubMedGoogle Scholar
  85. Nochez Y, Arsene S, Gueguen N, Chevrollier A, Ferre M, Guillet V, Desquiret V, Toutain A, Bonneau D, Procaccio V, Amati-Bonneau P, Pisella PJ, Reynier P (2009) Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect. J Mol Vis 15:598–608Google Scholar
  86. Pourova J, Kottova M, Voprsalova M, Pour M (2010) Reactive oxygen and nitrogen species in normal physiological processes. Acta Physiol (Oxf) 198(1):15–35Google Scholar
  87. Powers SK, Jackson MJ (2008) Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 88(4):1243–1276PubMedCentralPubMedGoogle Scholar
  88. Puigserver P, Spiegelman BM (2003) Peroxisome proliferators-activated receptor gamma coactivator 1α (PGC-1α): transcriptional coactivator and metabolic regulator. J Endocr Rev 24:78–90Google Scholar
  89. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. J Cell 92:829–839Google Scholar
  90. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY, Krauss S, Mootha VK, Lowell BB, Spiegelman BM (2001) Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. J Mol Cell 8:971–982Google Scholar
  91. Ramires P, Ji LL (2001) Glutathione supplementation and training increases myocardial resistance to ischemia-reperfusion in vivo. Am J Physiol 281:H679–H688Google Scholar
  92. Reid MB (2001) Redox modulation of skeletal muscle contraction: what we know and what we don’t. J Appl Physiol 90:724–731PubMedGoogle Scholar
  93. Russell AP (2005) PGC-1α and exercise: important partners in combating insulin resistance. J Curr Diabetes Rev 1:175–184Google Scholar
  94. Ryder J, Fahlman R, Wallberg-Henriksson H, Alessi D, Krook A, Zierath J (2000) Effect of contraction on mitogen-activated protein kinase signal transduction in skeletal muscle. J Biol Chem 275:1457–1462PubMedGoogle Scholar
  95. Santel A, Fuller MT (2001) Control of mitochondrial morphology by a human mitofusin. J Cell Sci 114:867–874PubMedGoogle Scholar
  96. Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88:611–638PubMedGoogle Scholar
  97. Schreiber SN, Emter R, Hock MB (2004) The estrogen-related receptor a (ERRα) functions in PPAR coactivator 1a (PGC-1α)-induced mitochondrial biogenesis. Proc Natl Acad Sci USA 101:6472–6477PubMedCentralPubMedGoogle Scholar
  98. Schulz E, Wenzel P, Münzel T, Daiber A (2012) Mitochondrial redox signaling: interaction of mitochondrial reactive oxygen species with other sources of oxidative stress. Antioxid redox signal. Jul 13 [Epub ahead of print]Google Scholar
  99. Sen CK (1995) Oxidants and antioxidants in exercise. J Appl Physiol 79:675–686PubMedGoogle Scholar
  100. Sen CK, Packer L (1996) Antioxidant and redox regulation of gene transcription. FASEB J 10(7):709–720PubMedGoogle Scholar
  101. Shi T, Wang F, Stieren E, Tong Q (2005) SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 280:13560–13567PubMedGoogle Scholar
  102. Sidell BD (1998) Intracellular oxygen diffusion: the roles of myoglobin and lipid at cold body temperature. J Exp Biol 201:1119–1128PubMedGoogle Scholar
  103. Song Z, Ghochani M, McCaffery JM, Frey TG, Chan DC (2009) Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. J Mol Biol Cell 20:3525–3532Google Scholar
  104. Soriano FX, Liesa M, Bach D, Chan DC, Palacin M, Zorzano A (2006) Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2. Diabetes 55:1783–1791PubMedGoogle Scholar
  105. St-Pierre J, Lin J, Krauss S (2003) Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 278:26597–26603PubMedGoogle Scholar
  106. St-Pierre J, Drori S, Uldry M (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408PubMedGoogle Scholar
  107. Taguchi N, Ishihara N, Jofuku A, Oka T, Mihara K (2007) Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem 282:11521–11529PubMedGoogle Scholar
  108. Valle I, Alvarez-Barrientos A, Arza E, Lamas S, Monsalve M (2005) PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovasc Res 66:562–573PubMedGoogle Scholar
  109. Vercauteren K, Pasko RA, Gleyzer N, Marino VM, Scarpulla RC (2006) PGC-1-related coactivator: immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth. Mol Cell Biol 26:7409–7419PubMedCentralPubMedGoogle Scholar
  110. Wasiak S, Zunino R, McBride HM (2007) Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J Cell Biol 177:439–450PubMedCentralPubMedGoogle Scholar
  111. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115:1111–1119PubMedCentralPubMedGoogle Scholar
  112. Wenz T, Rossi S, Rotundo RL (2009) Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci 106:20405–20410PubMedCentralPubMedGoogle Scholar
  113. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and function through the thermogenic coactivator PGC-1. Cell 98:115–124PubMedGoogle Scholar
  114. 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 USA 103:2653–2658PubMedCentralPubMedGoogle Scholar
  115. Zhang Y, Zhang GZ, Jiang N, Ma GD, Wen L, Bo H, Cao DN, Zhao F, Liu SS (2005) A feedback molecular regulation of uncoupling and ROS generation in muscular mitochondria during an acute exercise. Chin J Sport Med 24:389Google Scholar
  116. Zhou M, Lin BZ, Coughlin S, Vallega G, Pilch PF (2000) UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase. Am J Physiol Endocrinol Metab 279:622–629Google Scholar

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Laboratory of Physiological Hygiene and Exercise Science, School of KinesiologyUniversity of MinnesotaMinneapolisUSA

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