European Journal of Applied Physiology

, Volume 112, Issue 8, pp 3173–3177 | Cite as

Autophagy-related and autophagy-regulatory genes are induced in human muscle after ultraendurance exercise

  • Cécile Jamart
  • Nicolas Benoit
  • Jean-Marc Raymackers
  • Hyo Jeong Kim
  • Chang Keun Kim
  • Marc FrancauxEmail author
Short Communication


The purpose of this study was to evaluate whether ultra endurance exercise changes the mRNA levels of the autophagy-related and autophagy-regulatory genes. Eight men (44 ± 1 years, range: 38–50 years) took part in a 200-km running race. The average running time was 28 h 03 min ± 2 h 01 min (range: 22 h 15 min–35 h 04 min). A muscle sample was taken from the vastus lateralis 2 weeks prior to the race and 3 h after arrival. Gene expression was assessed by RT-qPCR. Transcript levels of autophagy-related genes were increased by 49% for ATG4b (P = 0.025), 57% for ATG12 (P = 0.013), 286% for Gabarapl1 (P = 0.008) and 103% for LC3b (P = 0.011). The lysosomal enzyme cathepsin L mRNA was upregulated by 123% (P = 0.003). Similarly, transcript levels of the autophagy-regulatory genes BNIP3 and BNIP3l were both increased by 113% (P = 0.031 and P = 0.007, respectively). Since upregulation of these genes has been related with an increased autophagic flux in various models, our results strongly suggest that autophagy is activated in response to ultra endurance exercise.


Endurance exercise Autophagy ATG BNIP3 Gabarapl1 LC3b 



This work was supported by the Fonds National de la Recherche Scientifique Médicale (FRSM 3.4574.03) (Belgium), by the Université Catholique de Louvain (FSR) and by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2010-413-G00007).

Conflict of interest

The authors have no conflict of interest to declare.


  1. Cabrera S, Marino G, Fernandez AF, Lopez-Otin C (2010) Autophagy, proteases and the sense of balance. Autophagy 6:961–963PubMedCrossRefGoogle Scholar
  2. de Lange P, Moreno M, Silvestri E, Lombardi A, Goglia F, Lanni A (2007) Fuel economy in food-deprived skeletal muscle: signaling pathways and regulatory mechanisms. Faseb J 21:3431–3441PubMedCrossRefGoogle Scholar
  3. Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie MJ, Francaux M (2008) Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. J Appl Physiol 104:371–378PubMedCrossRefGoogle Scholar
  4. Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Boncompagni S, Belia S, Wannenes F, Nicoletti C, Del Prete Z, Rosenthal N, Molinaro M, Protasi F, Fano G, Sandri M, Musaro A (2008) Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab 8:425–436PubMedCrossRefGoogle Scholar
  5. Eskelinen EL, Saftig P (2009) Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta 1793:664–673PubMedCrossRefGoogle Scholar
  6. Feng Z, Bai L, Yan J, Li Y, Shen W, Wang Y, Wertz K, Weber P, Zhang Y, Chen Y, Liu J (2011) Mitochondrial dynamic remodeling in strenuous exercise-induced muscle and mitochondrial dysfunction: regulatory effects of hydroxytyrosol. Free Radic Biol Med 50:1437–1446PubMedCrossRefGoogle Scholar
  7. Finn PF, Dice JF (2006) Proteolytic and lipolytic responses to starvation. Nutrition 22:830–844PubMedCrossRefGoogle Scholar
  8. Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, Kirshenbaum LA, Gottlieb RA, Gustafsson AB (2007) Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 14:146–157PubMedCrossRefGoogle Scholar
  9. Kim HJ, Jamart C, Deldicque L, An GL, Lee YH, Kim CK, Raymackers JM, Francaux M (2011) Endoplasmic reticulum stress markers and ubiquitin-proteasome pathway activity in response to a 200-km run. Med Sci Sports Exerc 43:18–25PubMedGoogle Scholar
  10. Klionsky DJ, Cregg JM, Dunn WA Jr, Emr SD, Sakai Y, Sandoval IV, Sibirny A, Subramani S, Thumm M, Veenhuis M, Ohsumi Y (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5:539–545PubMedCrossRefGoogle Scholar
  11. Lee EJ, Tournier C (2011) The requirement of uncoordinated 51-like kinase 1 (ULK1) and ULK2 in the regulation of autophagy. Autophagy 7:689–695PubMedCrossRefGoogle Scholar
  12. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J, Goldberg AL, Schiaffino S, Sandri M (2007) FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6:458–471PubMedCrossRefGoogle Scholar
  13. Mammucari C, Schiaffino S, Sandri M (2008) Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy 4:524–526PubMedGoogle Scholar
  14. McCully KK, Faulkner JA (1985) Injury to skeletal muscle fibers of mice following lengthening contractions. J Appl Physiol 59:119–126PubMedGoogle Scholar
  15. Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15:1101–1111PubMedCrossRefGoogle Scholar
  16. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26:9220–9231PubMedCrossRefGoogle Scholar
  17. Sahlin K, Shabalina IG, Mattsson CM, Bakkman L, Fernstrom M, Rozhdestvenskaya Z, Enqvist JK, Nedergaard J, Ekblom B, Tonkonogi M (2010) Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle. J Appl Physiol 108:780–787PubMedCrossRefGoogle Scholar
  18. Salminen A (1985) Lysosomal changes in skeletal muscles during the repair of exercise injuries in muscle fibers. Acta Physiol Scand Suppl 539:1–31PubMedGoogle Scholar
  19. Salminen A, Vihko V (1984) Autophagic response to strenuous exercise in mouse skeletal muscle fibers. Virchows Arch B Cell Pathol Incl Mol Pathol 45:97–106PubMedCrossRefGoogle Scholar
  20. Sandri M (2010) Autophagy in skeletal muscle. FEBS Lett 584:1411–1416PubMedCrossRefGoogle Scholar
  21. Tarnopolsky M (2004) Protein requirements for endurance athletes. Nutrition 20:662–668PubMedCrossRefGoogle Scholar
  22. Tracy K, Macleod KF (2007) Regulation of mitochondrial integrity, autophagy and cell survival by BNIP3. Autophagy 3:616–619PubMedGoogle Scholar
  23. Wang CW, Klionsky DJ (2003) The molecular mechanism of autophagy. Mol Med 9:65–76PubMedGoogle Scholar
  24. Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, Lecker SH, Goldberg AL (2007) FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 6:472–483PubMedCrossRefGoogle Scholar
  25. Zhao J, Brault JJ, Schild A, Goldberg AL (2008) Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy 4:378–380PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Cécile Jamart
    • 1
  • Nicolas Benoit
    • 1
  • Jean-Marc Raymackers
    • 1
  • Hyo Jeong Kim
    • 2
  • Chang Keun Kim
    • 2
  • Marc Francaux
    • 1
    Email author
  1. 1.Institute of Neuroscience, Research Group in Muscle and Exercise PhysiologyUniversité catholique de LouvainLouvain-la-NeuveBelgium
  2. 2.Department of Aging and Human PhysiologyKorea National Sport UniversitySongpa-guSouth Korea

Personalised recommendations