The impact of acute and chronic exercise on Nrf2 expression in relation to markers of mitochondrial biogenesis in human skeletal muscle

  • Hashim Islam
  • Jacob T. Bonafiglia
  • Patrick C. Turnbull
  • Craig A. Simpson
  • Christopher G. R. Perry
  • Brendon J. GurdEmail author
Original Article



To examine the relationship between changes in nuclear factor erythroid 2-related factor 2 (Nrf2) expression and markers of mitochondrial biogenesis in acutely and chronically exercised human skeletal muscle.


The impact of acute submaximal endurance (END) and supramaximal interval (Tabata) cycling on the upregulation of Nrf2 (and its downstream targets), nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM) mRNA expression was examined in healthy young males (n = 10). The relationship between changes in citrate synthase (CS) maximal activity and the protein content of Nrf2, heme oxygenase 1 (HO-1), NRF-1, and TFAM was also investigated following 4 weeks of Tabata in a separate group of males (n = 21).


Nrf2, NRF-1, and HO-1 mRNA expression increased after acute exercise (p < 0.05), whereas the increase in superoxide dismutase 2 (SOD2) mRNA expression approached significance (p = 0.08). Four weeks of Tabata increased CS activity and Nrf2, NRF-1, and TFAM protein content (p < 0.05), but decreased HO-1 protein content (p < 0.05). Training-induced changes in Nrf2 protein were strongly correlated with NRF-1 (r = 0.63, p < 0.01). When comparing protein content changes between individuals with the largest (HI: + 23%) and smallest (LO: − 1%) observed changes in CS activity (n = 8 each), increases in Nrf2 and TFAM protein content were apparent in the HI group only (p < 0.02) with medium-to-large effect sizes for between-group differences in changes in Nrf2 (ηp2=0.15) and TFAM (ηp2 = 0.12) protein content.


Altogether, our findings support a potential role for Nrf2 in exercise-induced mitochondrial biogenesis in human skeletal muscle.


NFE2L2 NRF-1 TFAM Mitochondrial content Sprint interval training Moderate-intensity continuous training 



We would like to thank Ali C. Dehghani for technical assistance with the cell culture experiments.

Author contribution

HI and BJG conceptualized and designed the study. Material preparation, data collection and analysis were performed by HI, JTB, PCT, and CAS. The first draft of the manuscript was written by HI. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.


Natural Sciences and Engineering Research Council of Canada (NSERC) with Grant numbers 402635 and PGS-D.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (TIFF 34,906 kb)
421_2019_4259_MOESM2_ESM.tiff (34.1 mb)
Supplementary material 2 (TIFF 34,906 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Kinesiology and Health StudiesQueen’s UniversityKingstonCanada
  2. 2.School of Kinesiology and Health ScienceYork UniversityTorontoCanada

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