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