Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

A Correction to this article is available

This article has been updated

Abstract

Physical inactivity represents the fourth leading risk factor for mortality, and it has been linked with a series of chronic disorders, the treatment of which absorbs ~ 85% of healthcare costs in developed countries. Conversely, physical activity promotes many health benefits; endurance exercise in particular represents a powerful stimulus to induce mitochondrial biogenesis, and it is routinely used to prevent and treat chronic metabolic disorders linked with sub-optimal mitochondrial characteristics. Given the importance of maintaining a healthy mitochondrial pool, it is vital to better characterize how manipulating the endurance exercise dose affects cellular mechanisms of exercise-induced mitochondrial biogenesis. Herein, we propose a definition of mitochondrial biogenesis and the techniques available to assess it, and we emphasize the importance of standardizing biopsy timing and the determination of relative exercise intensity when comparing different studies. We report an intensity-dependent regulation of exercise-induced increases in nuclear peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein content, nuclear phosphorylation of p53 (serine 15), and PGC-1α messenger RNA (mRNA), as well as training-induced increases in PGC-1α and p53 protein content. Despite evidence that PGC-1α protein content plateaus within a few exercise sessions, we demonstrate that greater training volumes induce further increases in PGC-1α (and p53) protein content, and that short-term reductions in training volume decrease the content of both proteins, suggesting training volume is still a factor affecting training-induced mitochondrial biogenesis. Finally, training-induced changes in mitochondrial transcription factor A (TFAM) protein content are regulated in a training volume-dependent manner and have been linked with training-induced changes in mitochondrial content.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Change history

  • 07 May 2018

    The original article can be found online at.

Notes

  1. 1.

    For interventions employing a mode of exercise for which power is not easily measurable (e.g., running or swimming), the same parameters can be determined, but velocity (v) is used instead of power.

References

  1. 1.

    Picard M, White K, Turnbull DM. Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study. J Appl Physiol. 2013;114(2):161–71.

    PubMed  Article  Google Scholar 

  2. 2.

    Cogswell AM, Stevens RJ, Hood DA. Properties of skeletal muscle mitochondria isolated from subsarcolemmal and intermyofibrillar regions. Am J Physiol Cell Physiol. 1993;264(2 33-2):C383–9.

    Article  CAS  Google Scholar 

  3. 3.

    Picard M, Shirihai OS, Gentil BJ, Burelle Y. Mitochondrial morphology transitions and functions: implications for retrograde signaling? Am J Physiol Regul Integr Comp Physiol. 2013;304(6):R393–406.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  4. 4.

    Handschin C, Spiegelman BM. Peroxisome proliferator-activated receptor γ coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev. 2006;27(7):728–35.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Kroemer G, Petit P, Zamzami N, Vayssiere J, Mignotte B. The biochemistry of programmed cell death. FASEB J. 1995;9(13):1277–87.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(2):335–44.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  7. 7.

    Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120(4):483–95.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Carter HN, Chen CC, Hood DA. Mitochondria, muscle health, and exercise with advancing age. Physiology. 2015;30(3):208–23.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Hesselink MK, Schrauwen-Hinderling V, Schrauwen P. Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus. Nat Rev Endocrinol. 2016;12(11):633–45.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148(6):1145–59.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  11. 11.

    McKenzie S, Phillips SM, Carter SL, Lowther S, Gibala MJ, Tarnopolsky MA. Endurance exercise training attenuates leucine oxidation and BCOAD activation during exercise in humans. Am J Physiol Endocrinol Metab. 2000;278(4 41-4):E580–7.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy. J Appl Physiol. 2002;93(1):3–30.

    PubMed  Article  Google Scholar 

  13. 13.

    Mogensen M, Sahlin K, Fernström M, Glintborg D, Vind BF, Beck-Nielsen H, et al. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes. 2007;56(6):1592–9.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Granata C, Oliveira RSF, Little JP, Renner K, Bishop DJ. Sprint-interval but not continuous exercise increases PGC-1α protein content and p53 phosphorylation in nuclear fractions of human skeletal muscle. Sci Rep. 2017;7:44227.

    PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ. An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1alpha and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1303–10.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Perry CGR, Lally J, Holloway GP, Heigenhauser GJF, Bonen A, Spriet LL. Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol. 2010;588(23):4795–810.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  17. 17.

    Wilkinson SB, Phillips SM, Atherton PJ, Patel R, Yarasheski KE, Tarnopolsky MA, et al. Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle. J Physiol. 2008;586(15):3701–17.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  18. 18.

    Granata C, Oliveira RSF, Little JP, Renner K, Bishop DJ. Mitochondrial adaptations to high-volume exercise training are rapidly reversed after a reduction in training volume in human skeletal muscle. FASEB J. 2016;30(10):3413–23.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Holloszy JO. Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem. 1967;242(9):2278–82.

    PubMed  CAS  Google Scholar 

  20. 20.

    Hoppeler H, Howald H, Conley K, Lindstedt SL, Claassen H, Vock P, et al. Endurance training in humans: aerobic capacity and structure of skeletal muscle. J Appl Physiol. 1985;59(2):320–7.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Jacobs RA, Lundby C. Mitochondria express enhanced quality as well as quantity in association with aerobic fitness across recreationally active individuals up to elite athletes. J Appl Physiol. 2013;114(3):344–50.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Zoll J, Sanchez H, N’Guessan B, Ribera F, Lampert E, Bigard X, et al. Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle. J Physiol. 2002;543(1):191–200.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  23. 23.

    WHO. Global health risks: mortality and burden of disease attributable to selected major risks (Geneva, Switzerland). Geneva: World Health Organization; 2009.

    Google Scholar 

  24. 24.

    Ding D, Lawson KD, Kolbe-Alexander TL, Finkelstein EA, Katzmarzyk PT, van Mechelen W, et al. The economic burden of physical inactivity: a global analysis of major non-communicable diseases. Lancet. 2016;388(10051):1311–24.

    PubMed  Article  Google Scholar 

  25. 25.

    Luft R. The development of mitochondrial medicine. Proc Natl Acad Sci USA. 1994;91(19):8731–8.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  26. 26.

    Stepien KM, Heaton R, Rankin S, Murphy A, Bentley J, Sexton D, et al. Evidence of oxidative stress and secondary mitochondrial dysfunction in metabolic and non-metabolic disorders. J Clin Med. 2017;6(7):71.

    PubMed Central  Article  Google Scholar 

  27. 27.

    Wang CH, Wang CC, Wei YH. Mitochondrial dysfunction in insulin insensitivity: implication of mitochondrial role in type 2 diabetes. Ann N Y Acad Sci. 2010;1201(1):157–65.

  28. 28.

    Miller BF, Hamilton KL. A perspective on the determination of mitochondrial biogenesis. Am J Physiol Endocrinol Metab. 2012;302(5):E496–9.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Short KR. Measuring mitochondrial protein synthesis to assess biogenesis. Am J Physiol Endocrinol Metab. 2012;302(9):E1153–4.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications. Annu Rev Biochem. 2007;76:701–22.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Drake JC, Wilson RJ, Yan Z. Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle. FASEB J. 2015;30(1):13–22.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  32. 32.

    Campello S, Strappazzon F, Cecconi F. Mitochondrial dismissal in mammals, from protein degradation to mitophagy. Biochim Biophys Acta, Bioenerg. 2014;1837(4):451–60.

    Article  CAS  Google Scholar 

  33. 33.

    Wasilewski M, Scorrano L. The changing shape of mitochondrial apoptosis. Trends Endocrinol Metab. 2009;20(6):287–94.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Medeiros DM. Assessing mitochondria biogenesis. Methods. 2008;46(4):288–94.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Atherton PJ, Phillips BE, Wilkinson DJ. Exercise and regulation of protein metabolism. Prog Mol Biol Transl Sci. 2015;135:75–98.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Bishop DJ, Granata C, Eynon N. Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content? Biochim Biophys Acta Gen Subj. 2014;1840(4):1266–75.

    Article  CAS  Google Scholar 

  37. 37.

    Ritov VB, Menshikova EV, Kelley DE. Analysis of cardiolipin in human muscle biopsy. J Chromatogr B Biomed Sci Appl. 2006;831(1):63–71.

    CAS  Google Scholar 

  38. 38.

    Kraunsøe R, Boushel R, Hansen CN, Schjerling P, Qvortrup K, Støckel M, et al. Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity. J Physiol. 2010;588(12):2023–32.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  39. 39.

    Larsen S, Nielsen J, Hansen CN, Nielsen LB, Wibrand F, Stride N, et al. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol. 2012;590(14):3349–60.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  40. 40.

    Reichmann H, Hoppeler H, Mathieu-Costello O, Von Bergen F, Pette D. Biochemical and ultrastructural changes of skeletal muscle mitochondria after chronic electrical stimulation in rabbits. Pflügers Archiv. 1985;404(1):1–9.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Johnson ML, Robinson MM, Nair KS. Skeletal muscle aging and the mitochondrion. Trends Endocrinol Metab. 2013;24(5):247–56.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. 42.

    Granata C, Oliveira RSF, Little JP, Renner K, Bishop DJ. Training intensity modulates changes in PGC-1α and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle. FASEB J. 2016;30(2):959–70.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Montero D, Cathomen A, Jacobs RA, Flück D, de Leur J, Keiser S, et al. Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training. J Physiol. 2015;593(20):4677–88.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  44. 44.

    Rowe G, Patten I, Zsengeller ZK, El-Khoury R, Okutsu M, Bampoh S, et al. Disconnecting mitochondrial content from respiratory chain capacity in PGC-1-deficient skeletal muscle. Cell Rep. 2013;3(5):1449–56.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  45. 45.

    Tonkonogi M, Sahlin K. Physical exercise and mitochondrial function in human skeletal muscle. Exerc Sport Sci Rev. 2002;30(3):129–37.

    PubMed  Article  Google Scholar 

  46. 46.

    Lanza IR, Nair KS. Mitochondrial metabolic function assessed in vivo and in vitro. Curr Opin Clin Nutr Metab Care. 2010;13(5):511–7.

    PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Picard M, Taivassalo T, Ritchie D, Wright KJ, Thomas MM, Romestaing C, et al. Mitochondrial structure and function are disrupted by standard isolation methods. PLoS One. 2011;6(3):18317.

    Article  CAS  Google Scholar 

  48. 48.

    Hood DA. Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Appl Physiol Nutr Metab. 2009;34(3):465–72.

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Hornberger TA, Carter HN, Figueiredo VC, Camera DM, Chaillou T, Nader GA, et al. Commentaries on viewpoint: the rigorous study of exercise adaptations: why mRNA might not be enough. J Appl Physiol. 2016;121(2):597–600.

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    Miller BF, Konopka AR, Hamilton KL. The rigorous study of exercise adaptations: why mRNA might not be enough. J Appl Physiol. 2016;121(2):594–6.

    PubMed  Article  Google Scholar 

  51. 51.

    Miller BF, Konopka AR, Hamilton KL. Last Word on Viewpont: on the rigorous study of exercise adaptations: why mRNA might not be enough? J Appl Physiol. 2016;121(2):601.

    PubMed  Article  Google Scholar 

  52. 52.

    Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, et al. Global quantification of mammalian gene expression control. Nature. 2011;473(7347):337–42.

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Seiler S, Tønnessen E. Intervals, thresholds, and long slow distance: the role of intensity and duration in endurance training. Sportscience. 2009;13:32–53.

    Google Scholar 

  54. 54.

    Astrand PO, Rodahl K. Textbook of work physiology. New York: McGraw Hill; 1986.

    Google Scholar 

  55. 55.

    Bentley DJ, Newell J, Bishop D. Incremental exercise test design and analysis: Implications for performance diagnostics in endurance athletes. Sports Med. 2007;37(7):575–86.

    PubMed  Article  Google Scholar 

  56. 56.

    Adami A, Sivieri A, Moia C, Perini R, Ferretti G. Effects of step duration in incremental ramp protocols on peak power and maximal oxygen consumption. Eur J Appl Physiol. 2013;113(10):2647–53.

    PubMed  Article  Google Scholar 

  57. 57.

    Morton RH. Why peak power is higher at the end of steeper ramps: an explanation based on the “critical power” concept. J Sports Sci. 2011;29(3):307–9.

    PubMed  Article  Google Scholar 

  58. 58.

    Weston KS, Wisløff U, Coombes JS. High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. Br J Sports Med. 2014;48(16):1227–34.

    PubMed  Article  Google Scholar 

  59. 59.

    Girard O, Mendez-Villanueva A, Bishop D. Repeated-sprint ability—part I. Sports Med. 2011;41(8):673–94.

    PubMed  Article  Google Scholar 

  60. 60.

    Jacobs RA, Flück D, Bonne TC, Bürgi S, Christensen PM, Toigo M, et al. Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function. J Appl Physiol. 2013;115(6):785–93.

    PubMed  Article  Google Scholar 

  61. 61.

    Rose AJ, Kiens B, Richter EA. Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise. J Physiol. 2006;574(3):889–903.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  62. 62.

    Lima TI, Araujo HN, Menezes ES, Sponton CH, Araújo MB, Bomfim LH, et al. Role of microRNAs on the regulation of mitochondrial biogenesis and insulin signaling in skeletal muscle. J Cell Physiol. 2017;232(5):958–66.

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    Safdar A, Abadi A, Akhtar M, Hettinga BP, Tarnopolsky MA. miRNA in the regulation of skeletal muscle adaptation to acute endurance exercise in C57Bl/6J male mice. PLoS One. 2009;4(5):e5610.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  64. 64.

    Baggish AL, Hale A, Weiner RB, Lewis GD, Systrom D, Wang F, et al. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol. 2011;589(16):3983–94.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  65. 65.

    Russell AP, Lamon S, Boon H, Wada S, Güller I, Brown EL, et al. Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training. J Physiol. 2013;591(18):4637–53.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  66. 66.

    Ling C, Groop L. Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes. 2009;58(12):2718–25.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  67. 67.

    Ling C, Rönn T. Epigenetic adaptation to regular exercise in humans. Drug Discovery Today. 2014;19(7):1015–8.

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Barres R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012;15(3):405–11.

    PubMed  Article  CAS  Google Scholar 

  69. 69.

    Voisin S, Eynon N, Yan X, Bishop D. Exercise training and DNA methylation in humans. Acta Physiol. 2015;213(1):39–59.

    Article  CAS  Google Scholar 

  70. 70.

    Nitert MD, Dayeh T, Volkov P, Elgzyri T, Hall E, Nilsson E, et al. Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes. 2012;61(12):3322–32.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  71. 71.

    Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 2013;17(2):162–84.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  72. 72.

    McGinley C, Bishop DJ. Distinct protein and mRNA kinetics of skeletal muscle proton transporters following exercise can influence interpretation of adaptations to training. Exp Physiol. 2016;101(12):1565–80.

    PubMed  Article  CAS  Google Scholar 

  73. 73.

    Gibala MJ, Little JP, Macdonald MJ, Hawley JA. Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol. 2012;590(5):1077–84.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  74. 74.

    Hawley JA, Hargreaves M, Joyner MJ, Zierath JR. Integrative biology of exercise. Cell. 2014;159(4):738–49.

    PubMed  Article  CAS  Google Scholar 

  75. 75.

    Saleem A, Carter HN, Iqbal S, Hood DA. Role of p53 within the regulatory network controlling muscle mitochondrial biogenesis. Exerc Sport Sci Rev. 2011;39(4):199–205.

    PubMed  Google Scholar 

  76. 76.

    Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α): transcriptional coactivator and metabolic regulator. Endocr Rev. 2003;24(1):78–90.

    PubMed  Article  CAS  Google Scholar 

  77. 77.

    Vainshtein A, Tryon LD, Pauly M, Hood DA. Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am J Physiol Cell Physiol. 2015;308(9):C710–9.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  78. 78.

    Geng T, Li P, Okutsu M, Yin X, Kwek J, Zhang M, et al. PGC-1alpha 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. 2010;298(3):C572–9.

    PubMed  Article  CAS  Google Scholar 

  79. 79.

    Leick L, Wojtaszewski JFP, Johansen ST, Kiilerich K, Comes G, Hellsten Y, et al. PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2008;294(2):E463–74.

    PubMed  Article  CAS  Google Scholar 

  80. 80.

    Canto C, Auwerx J. PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol. 2009;20(2):98–105.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  81. 81.

    Jäger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc Natl Acad Sci USA. 2007;104(29):12017–22.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  82. 82.

    Bartlett JD, Joo CH, Jeong TS, Louhelainen J, Cochran AJ, Gibala MJ, et al. Matched work high-intensity interval and continuous running induce similar increases in PGC-1α mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. J Appl Physiol. 2012;112(7):1135–43.

    PubMed  Article  CAS  Google Scholar 

  83. 83.

    Cochran AJR, Percival ME, Tricarico S, Little JP, Cermak N, Gillen JB, et al. Intermittent and continuous high-intensity exercise training induce similar acute but different chronic muscle adaptations. Exp Physiol. 2014;99(5):782–91.

    PubMed  Article  CAS  Google Scholar 

  84. 84.

    Egan B, Carson BP, Garcia-Roves PM, Chibalin AV, Sarsfield FM, Barron N, et al. Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor γ coactivator-1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. J Physiol. 2010;588(10):1779–90.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  85. 85.

    Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle. J Appl Physiol. 2009;106(3):929–34.

    PubMed  Article  CAS  Google Scholar 

  86. 86.

    Little JP, Safdar A, Cermak N, Tarnopolsky MA, Gibala MJ. Acute endurance exercise increases the nuclear abundance of PGC-1α in trained human skeletal muscle. Am J Physiol Endocrinol Metab. 2010;298(4):R912–7.

    CAS  Google Scholar 

  87. 87.

    Brandt N, Gunnarsson TP, Hostrup M, Tybirk J, Nybo L, Pilegaard H, et al. Impact of adrenaline and metabolic stress on exercise-induced intracellular signaling and PGC-1α mRNA response in human skeletal muscle. Physiol Rep. 2016;4(14):12844.

    Article  CAS  Google Scholar 

  88. 88.

    Aquilano K, Vigilanza P, Baldelli S, Pagliei B, Rotilio G, Ciriolo MR. Peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha) and sirtuin 1 (SIRT1) reside in mitochondria-possible direct function in mitochondrial biogenesis. J Biol Chem. 2010;285(28):21590–9.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  89. 89.

    Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression. J Biol Chem. 2007;282(1):194–9.

    PubMed  Article  CAS  Google Scholar 

  90. 90.

    Safdar A, Little JP, Stokl AJ, Hettinga BP, Akhtar M, Tarnopolsky MA. Exercise increases mitochondrial PGC-1α content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J Biol Chem. 2011;286(12):10605–17.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  91. 91.

    Heesch MW, Shute RJ, Kreiling JL, Slivka DR. Transcriptional control, but not subcellular location, of PGC-1α is altered following exercise in a hot environment. J Appl Physiol. 2016;121(3):741–9.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  92. 92.

    McGee SL, Hargreaves M. Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle. Diabetes. 2004;53(5):1208–14.

    PubMed  Article  CAS  Google Scholar 

  93. 93.

    Tachtsis B, Smiles W, Lane S, Hawley J, Camera DM. Acute endurance exercises induces nuclear p53 abundance in human skeletal muscle. Front Physiol. 2016;7:144.

    PubMed  PubMed Central  Article  Google Scholar 

  94. 94.

    Dumke CL, Davis JM, Murphy EA, Nieman DC, Carmichael MD, Quindry JC, et al. Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis. Eur J Appl Physiol. 2009;107(4):419–27.

    PubMed  Article  CAS  Google Scholar 

  95. 95.

    Mathai AS, Bonen A, Benton CR, Robinson DL, Graham TE. Rapid exercise-induced changes in PGC-1α mRNA and protein in human skeletal muscle. J Appl Physiol. 2008;105(4):1098–105.

    PubMed  Article  CAS  Google Scholar 

  96. 96.

    Nordsborg NB, Lundby C, Leick L, Pilegaard H. Relative workload determines exercise-induced increases in PGC-1α mRNA. Med Sci Sports Exerc. 2010;42(8):1477–84.

    PubMed  Article  CAS  Google Scholar 

  97. 97.

    Russell AP, Hesselink MKC, Lo SK, Schrauwen P. Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. FASEB J. 2005;19(8):986–8.

    PubMed  Article  CAS  Google Scholar 

  98. 98.

    Vissing K, McGee SL, Roepstorff C, Schjerling P, Hargreaves M, Kiens B. Effect of sex differences on human MEF2 regulation during endurance exercise. Am J Physiol Endocrinol Metab. 2008;294(2):E408–15.

    PubMed  Article  CAS  Google Scholar 

  99. 99.

    Watt MJ, Southgate RJ, Holmes AG, Febbraio MA. Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) α and δ and PPAR coactivator 1α in human skeletal muscle, but not lipid regulatory genes. J Mol Endocrinol. 2004;33(2):533–44.

    PubMed  Article  CAS  Google Scholar 

  100. 100.

    Cartoni R, Léger B, Hock MB, Praz M, Crettenand A, Pich S, et al. Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise. J Physiol. 2005;567(1):349–58.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  101. 101.

    Cluberton LJ, McGee SL, Murphy RM, Hargreaves M. Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression. J Appl Physiol. 2005;99(4):1359–63.

    PubMed  Article  CAS  Google Scholar 

  102. 102.

    Cochran AJR, Little JP, Tarnopolsky MA, Gibala MJ. Carbohydrate feeding during recovery alters the skeletal muscle metabolic response to repeated sessions of high-intensity interval exercise in humans. J Appl Physiol. 2010;108(3):628–36.

    PubMed  Article  CAS  Google Scholar 

  103. 103.

    Pilegaard H, Osada T, Andersen LT, Helge JW, Saltin B, Neufer PD. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. Metabolism. 2005;54(8):1048–55.

    PubMed  Article  CAS  Google Scholar 

  104. 104.

    Sriwijitkamol A, Coletta DK, Wajcberg E, Balbontin GB, Reyna SM, Barrientes J, et al. Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study. Diabetes. 2007;56(3):836–48.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  105. 105.

    Popov DV, Lysenko EA, Vepkhvadze TF, Kurochkina NS, Maknovskii PA, Vinogradova OL. Promoter-specific regulation of PPARGC1A gene expression in human skeletal muscle. J Mol Endocrinol. 2015;55(2):159–68.

    PubMed  Article  CAS  Google Scholar 

  106. 106.

    Allan R, Sharples AP, Close GL, Drust B, Shepherd SO, Dutton J, et al. Postexercise cold water immersion modulates skeletal muscle PGC-1α mRNA expression in immersed and nonimmersed limbs: evidence of systemic regulation. J Appl Physiol. 2017;123(2):451–9.

    PubMed  Article  Google Scholar 

  107. 107.

    Broatch JR, Petersen A, Bishop DJ. Cold-water immersion following sprint interval training does not alter endurance signaling pathways or training adaptations in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2017;313(4):R372–84.

    PubMed  Article  CAS  Google Scholar 

  108. 108.

    Joo CH, Allan R, Drust B, Close GL, Jeong TS, Bartlett JD, et al. Passive and post-exercise cold-water immersion augments PGC-1alpha and VEGF expression in human skeletal muscle. Eur J Appl Physiol. 2016;116(11–12):2315–26.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  109. 109.

    Egan B, O’Connor PL, Zierath JR, O’Gorman DJ. Time course analysis reveals gene-specific transcript and protein kinetics of adaptation to short-term aerobic exercise training in human skeletal muscle. PLoS One. 2013;8(9):e74092.

    Article  CAS  Google Scholar 

  110. 110.

    Leick L, Plomgaard P, Grønløkke L, Al-Abaiji F, Wojtaszewski JFP, Pilegaard H. Endurance exercise induces mRNA expression of oxidative enzymes in human skeletal muscle late in recovery. Scand J Med Sci Sports. 2010;20(4):593–9.

    PubMed  Article  CAS  Google Scholar 

  111. 111.

    Edgett BA, Foster WS, Hankinson PB, Simpson CA, Little JP, Graham RB, et al. Dissociation of increases in PGC-1α and its regulators from exercise intensity and muscle activation following acute exercise. PLoS One. 2013;8(8):e71623.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  112. 112.

    Wang L, Psilander N, Tonkonogi M, Ding S, Sahlin K. Similar expression of oxidative genes after interval and continuous exercise. Med Sci Sports Exerc. 2009;41(12):2136–44.

    PubMed  Article  CAS  Google Scholar 

  113. 113.

    Popov D, Zinovkin R, Karger E, Tarasova O, Vinogradova O. Effects of continuous and intermittent aerobic exercise upon mRNA expression of metabolic genes in human skeletal muscle. J Sports Med Phys Fitness. 2014;54(3):362–9.

    PubMed  CAS  Google Scholar 

  114. 114.

    Morrison D, Hughes J, Della Gatta PA, Mason S, Lamon S, Russell AP, et al. Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans. Free Radic Biol Med. 2015;89:852–62.

    PubMed  Article  CAS  Google Scholar 

  115. 115.

    Stepto NK, Benziane B, Wadley GD, Chibalin AV, Canny BJ, Eynon N, et al. Short-term intensified cycle training alters acute and chronic responses of PGC1α and cytochrome c oxidase IV to exercise in human skeletal muscle. PLoS One. 2012;7(12):e53080.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  116. 116.

    Coffey VG, Zhong Z, Shield A, Canny BJ, Chibalin AV, Zierath JR, et al. Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. FASEB J. 2006;20(1):190–2.

    PubMed  Article  CAS  Google Scholar 

  117. 117.

    De Filippis E, Alvarez G, Berria R, Cusi K, Everman S, Meyer C, et al. Insulin-resistant muscle is exercise resistant: evidence for reduced response of nuclear-encoded mitochondrial genes to exercise. Am J Physiol Endocrinol Metab. 2008;294(3):E607–14.

    PubMed  Article  CAS  Google Scholar 

  118. 118.

    Edgett BA, Bonafiglia JT, Baechler BL, Quadrilatero J, Gurd BJ. The effect of acute and chronic sprint-interval training on LRP130, SIRT3, and PGC-1α expression in human skeletal muscle. Physiol Rep. 2016;4(17):e12879.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  119. 119.

    Larsen FJ, Schiffer TA, Ørtenblad N, Zinner C, Morales-Alamo D, Willis SJ, et al. High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation. FASEB J. 2016;30(1):417–27.

    PubMed  Article  CAS  Google Scholar 

  120. 120.

    Little JP, Safdar A, Wilkin GP, Tarnopolsky MA, Gibala MJ. A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: Potential mechanisms. J Physiol. 2010;588(6):1011–22.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  121. 121.

    Vincent G, Lamon S, Gant N, Vincent P, MacDonald J, Markworth J, et al. Changes in mitochondrial function and mitochondria associated protein expression in response to 2-weeks of high intensity interval training. Front Physiol. 2015;6:51.

    PubMed  PubMed Central  Google Scholar 

  122. 122.

    Burgomaster KA, Howarth KR, Phillips SM, Rakobowchuk M, Macdonald MJ, McGee SL, et al. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J Physiol. 2008;586(1):151–60.

    PubMed  Article  CAS  Google Scholar 

  123. 123.

    Gurd BJ, Perry CG, Heigenhauser GJ, Spriet LL, Bonen A. High-intensity interval training increases SIRT1 activity in human skeletal muscle. Appl Physiol Nutr Metab. 2010;35(3):350–7.

    PubMed  Article  CAS  Google Scholar 

  124. 124.

    Gurd BJ, Yoshida Y, McFarlan JT, Holloway GP, Moyes CD, Heigenhauser GJF, et al. Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011;301(1):R67–75.

    PubMed  Article  CAS  Google Scholar 

  125. 125.

    Hood MS, Little JP, Tarnopolsky MA, Myslik F, Gibala MJ. Low-volume interval training improves muscle oxidative capacity in sedentary adults. Med Sci Sports Exerc. 2011;43(10):1849–56.

    PubMed  Article  CAS  Google Scholar 

  126. 126.

    Konopka AR, Suer MK, Wolff CA, Harber MP. Markers of human skeletal muscle mitochondrial biogenesis and quality control: Effects of age and aerobic exercise training. J Gerontol A Biol Sci Med Sci. 2014;69(4):371–8.

    PubMed  Article  CAS  Google Scholar 

  127. 127.

    Scalzo RL, Peltonen GL, Binns SE, Shankaran M, Giordano GR, Hartley DA, et al. Greater muscle protein synthesis and mitochondrial biogenesis in males compared with females during sprint interval training. FASEB J. 2014;28(6):2705–14.

    PubMed  Article  CAS  Google Scholar 

  128. 128.

    Irving BA, Lanza IR, Henderson GC, Rao RR, Spiegelman BM, Sreekumaran Nair K. Combined training enhances skeletal muscle mitochondrial oxidative capacity independent of age. J Clin Endocrinol Metab. 2015;100(4):1654–63.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  129. 129.

    Levine AJ, Hu W, Feng Z. The P53 pathway: what questions remain to be explored? Cell Death Differ. 2006;13(6):1027–36.

    PubMed  Article  CAS  Google Scholar 

  130. 130.

    Oren M. Regulation of the p53 tumor suppressor protein. J Biol Chem. 1999;274(51):36031–4.

    PubMed  Article  CAS  Google Scholar 

  131. 131.

    Vousden KH, Ryan KM. P53 and metabolism. Nat Rev Cancer. 2009;9(10):691–700.

    PubMed  Article  CAS  Google Scholar 

  132. 132.

    Saleem A, Carter HN, Hood DA. P53 is necessary for the adaptive changes in cellular milieu subsequent to an acute bout of endurance exercise. Am J Physiol Cell Physiol. 2014;306(3):C241–9.

    PubMed  Article  CAS  Google Scholar 

  133. 133.

    Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, et al. p53 regulates mitochondrial respiration. Science. 2006;312(5780):1650–3.

    PubMed  Article  CAS  Google Scholar 

  134. 134.

    Park JY, Wang PY, Matsumoto T, Sung HJ, Ma W, Choi JW, et al. P53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res. 2009;105(7):705–12.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  135. 135.

    Saleem A, Adhihetty PJ, Hood DA. Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle. Physiol Genomics. 2009;37(1):58–66.

    PubMed  Article  CAS  Google Scholar 

  136. 136.

    Bergeaud M, Mathieu L, Guillaume A, Moll UM, Mignotte B, Le Floch N, et al. Mitochondrial p53 mediates a transcription-independent regulation of cell respiration and interacts with the mitochondrial F1F0-ATP synthase. Cell Cycle. 2013;12(17):3781–93.

    Article  CAS  Google Scholar 

  137. 137.

    Stambolsky P, Weisz L, Shats I, Klein Y, Goldfinger N, Oren M, et al. Regulation of AIF expression by p53. Cell Death Differ. 2006;13(12):2140–9.

    PubMed  Article  CAS  Google Scholar 

  138. 138.

    Vahsen N, Candé C, Brière JJ, Bénit P, Joza N, Larochette N, et al. AIF deficiency compromises oxidative phosphorylation. EMBO J. 2004;23(23):4679–89.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  139. 139.

    Li J, Donath S, Li Y, Qin D, Prabhakar BS, Li P. miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genetics. 2010;6(1):e1000795.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  140. 140.

    Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, et al. The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet. 2005;14(11):1405–15.

    PubMed  Article  CAS  Google Scholar 

  141. 141.

    Wang W, Cheng X, Lu J, Wei J, Fu G, Zhu F, et al. Mitofusin-2 is a novel direct target of p53. Biochem Biophys Res Commun. 2010;400(4):587–92.

    PubMed  Article  CAS  Google Scholar 

  142. 142.

    Irrcher I, Ljubicic V, Kirwan AF, Hood DA. AMP-activated protein kinase-regulated activation of the PGC-1α promoter in skeletal muscle cells. PLoS One. 2008;3(10):e3614.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  143. 143.

    Bartlett JD, Close GL, Drust B, Morton JP. The emerging role of p53 in exercise metabolism. Sports Med. 2014;44(3):303–9.

    PubMed  Article  Google Scholar 

  144. 144.

    Stocks B, Dent JR, Joanisse S, McCurdy CE, Philp A. Skeletal muscle fibre-specific knockout of p53 does not reduce mitochondrial content or enzyme activity. Front Physiol. 2017;8:941.

    PubMed  PubMed Central  Article  Google Scholar 

  145. 145.

    Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 1997;91(3):325–34.

    PubMed  Article  CAS  Google Scholar 

  146. 146.

    Marchenko ND, Hanel W, Li D, Becker K, Reich N, Moll UM. Stress-mediated nuclear stabilization of p53 is regulated by ubiquitination and importin-α3 binding. Cell Death Differ. 2010;17(2):255–67.

    PubMed  Article  CAS  Google Scholar 

  147. 147.

    Saleem A, Hood DA. Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53-tfam-mitochondrial DNA complex in skeletal muscle. J Physiol. 2013;591(14):3625–36.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  148. 148.

    Zhuang J, Kamp WM, Li J, Liu C, Kang J-G, P-y Wang, et al. Forkhead box O3A (FOXO3) and the mitochondrial disulfide relay carrier (CHCHD4) regulate p53 protein nuclear activity in response to exercise. J Biol Chem. 2016;291(48):24819–27.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  149. 149.

    Chen YW, Nader GA, Baar KR, Fedele MJ, Hoffman EP, Esser KA. Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling. J Physiol. 2002;545(1):27–41.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  150. 150.

    Philp A, Schenk S. Unraveling the complexities of sirt1-mediated mitochondrial regulation in skeletal muscle. Exerc Sport Sci Rev. 2013;41(3):174–81.

    PubMed  PubMed Central  Article  Google Scholar 

  151. 151.

    Bartlett JD, Louhelainen J, Iqbal Z, Cochran AJ, Gibala MJ, Gregson W, et al. Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis. Am J Physiol Regul Integr Comp Physiol. 2013;304(6):R450–8.

    PubMed  Article  CAS  Google Scholar 

  152. 152.

    Hammond KM, Impey SG, Currell K, Mitchell N, Shepherd SO, Jeromson S, et al. Postexercise high-fat feeding suppresses p70S6K1 activity in human skeletal muscle. Med Sci Sports Exerc. 2016;48(11):2108–17.

    PubMed  Article  CAS  Google Scholar 

  153. 153.

    Scarpulla RC. Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta Gene Struct Express. 2002;1576(1–2):1–14.

    Article  CAS  Google Scholar 

  154. 154.

    Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab. 2012;23(9):459–66.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  155. 155.

    Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98(1):115–24.

    PubMed  Article  CAS  Google Scholar 

  156. 156.

    Pilegaard H, Saltin B, Neufer DP. Exercise induces transient transcriptional activation of the PGC-1α gene in human skeletal muscle. J Physiol. 2003;546(3):851–8.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  157. 157.

    Norrbom J, Sundberg CJ, Ameln H, Kraus WE, Jansson E, Gustafsson T. PGC-1α mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle. J Appl Physiol. 2004;96(1):189–94.

    PubMed  Article  CAS  Google Scholar 

  158. 158.

    Slivka D, Heesch M, Dumke C, Cuddy J, Hailes W, Ruby B. Effects of post-exercise recovery in a cold environment on muscle glycogen, PGC-1 alpha, and downstream transcription factors. Cryobiology. 2013;66(3):250–5.

    PubMed  Article  CAS  Google Scholar 

  159. 159.

    Jensen L, Gejl KD, Ørtenblad N, Nielsen JL, Bech RD, Nygaard T, et al. Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes. Physiol Rep. 2015;3(2):e12184.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  160. 160.

    Mendham AE, Duffield R, Coutts AJ, Marino F, Boyko A, Bishop DJ. Rugby-specific small-sided games training is an effective alternative to stationary cycling at reducing clinical risk factors associated with the development of type 2 diabetes: A randomized, controlled trial. PLoS One. 2015;10(6):e0127548.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  161. 161.

    Psilander N, Frank P, Flockhart M, Sahlin K. Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle. Eur J Appl Physiol. 2013;113(4):951–63.

    PubMed  Article  CAS  Google Scholar 

  162. 162.

    Psilander N, Wang L, Westergren J, Tonkonogi M, Sahlin K. Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise. Eur J Appl Physiol. 2010;110(3):607.

    Article  Google Scholar 

  163. 163.

    Montoya J, Perez-Martos A, Garstka HL, Wiesner RJ. Regulation of mitochondrial transcription by mitochondrial transcription factor A. Mol Cell Biochem. 1997;174(1–2):227–30.

    PubMed  Article  CAS  Google Scholar 

  164. 164.

    Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, et al. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet. 1998;18(3):231–6.

    PubMed  Article  CAS  Google Scholar 

  165. 165.

    Gordon JW, Rungi AA, Inagaki H, Hood DA. Selected contribution: Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle. J Appl Physiol. 2001;90(1):389–96.

    PubMed  Article  CAS  Google Scholar 

  166. 166.

    Popov DV, Zinovkin RA, Karger EM, Tarasova OS, Vinogradova OL. The effect of aerobic exercise on the expression of genes in skeletal muscles of trained and untrained men. Hum Physiol. 2013;39(2):190–5.

    Article  CAS  Google Scholar 

  167. 167.

    Bengtsson J, Gustafsson T, Widegren U, Jansson E, Sundberg CJ. Mitochondrial transcription factor A and respiratory complex IV increase in response to exercise training in humans. Pflugers Arch. 2001;443(1):61–6.

    PubMed  Article  CAS  Google Scholar 

  168. 168.

    Mahoney DJ, Parise G, Melov S, Safdar A, Tarnopolsky MA. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB J. 2005;19(11):1498–500.

    PubMed  Article  CAS  Google Scholar 

  169. 169.

    Metcalfe R, Koumanov F, Ruffino J, Stokes K, Holman G, Thompson D, et al. Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT). Eur J Appl Physiol. 2015;115(11):2321–34.

    PubMed  Article  CAS  Google Scholar 

  170. 170.

    Slivka DR, Dumke CL, Tucker TJ, Cuddy JS, Ruby B. Human mRNA response to exercise and temperature. Int J Sports Med. 2012;33(2):94–100.

    PubMed  Article  CAS  Google Scholar 

  171. 171.

    Slivka DR, Heesch MWS, Dumke CL, Cuddy JS, Hailes WS, Ruby BC. Human skeletal muscle mRNA response to a single hypoxic exercise bout. Wilderness Environ Med. 2014;25(4):462–5.

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Cesare Granata.

Ethics declarations

Funding

No sources of funding were used to assist in the preparation of this manuscript.

Conflicts of Interest

Cesare Granata, Nicholas Jamnick, and David Bishop have no conflicts of interest relevant to the content of this review.

Author Contributions

Cesare Granata conducted the literature searches. Cesare Granata, Nicholas Jamnick, and David Bishop analysed and interpreted the data. Cesare Granata wrote the manuscript. Cesare Granata, Nicholas Jamnick, and David Bishop critically revised and contributed to the manuscript. Cesare Granata and David Bishop have primary responsibility for the final content. Data analysis took place at Victoria University. All persons designated as authors qualify for authorship, and all those qualifying for authorship are listed. All authors read and approved the final manuscript.

Acknowledgements

The authors acknowledge Dr. Cian McGinley, Mr. Alessandro Garofolini, Dr. Sarah Voisin, and Mr. Ramón Rodriguez for their valuable help with data analysis and presentation and their constructive critique of this manuscript. Space limitations mean we were unable to cite a number of outstanding contributions from authors who have greatly enhanced this field of research; therefore, we have chosen to refer to review articles where available. We apologize to those authors who were not cited in this manuscript.

Additional information

The original version of this article was revised: Due to error in Section 3.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 174 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Granata, C., Jamnick, N.A. & Bishop, D.J. Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis. Sports Med 48, 1541–1559 (2018). https://doi.org/10.1007/s40279-018-0894-4

Download citation