Mitochondrial Biogenesis in Human Skeletal Muscle: High-Intensity Interval Training Versus Moderate-Intensity Continuous Training
- 1Department of Sport and Human Movement Science, Section for Nutrition, Exercise and Health, University of Vienna, 1150 Vienna, Austria
Abstract
Mitochondrial biogenesis is a hallmark adaptation to endurance exercise with broad implications for metabolic health and athletic performance. High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) both stimulate mitochondrial remodeling in human skeletal muscle, yet whether exercise intensity or total work performed is the principal determinant remains contested. This mini review synthesizes current evidence on the intensity-dependent activation of AMP-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)—a central transcriptional coactivator in mitochondrial biogenesis. The author critically examines the distinction between mitochondrial content and respiratory function, discusses how study design—particularly work-matched versus time-matched protocols—shapes comparative conclusions, and identifies key unresolved questions including sex-based differences, fiber-type specificity, and the role of mitochondrial dynamics. The evidence indicates that both modalities are effective but operate through overlapping yet intensity-sensitive mechanisms; the metabolic-stress hypothesis provides a testable explanatory framework. Practical implications for exercise prescription are discussed. The review further considers the coordination of mitochondrial translation and turnover, mitochondrial Ca2+ handling, sex-specific evidence limitations, and translational outcomes in cardiometabolic disease.
Related
- High-intensity interval training and moderate-intensity continuous training versus usual care in adults with familial hypercholesterolaemia: protocol for the UPPA-FH three-arm randomised trial
- High-intensity interval versus moderate-intensity continuous freestyle swimming in obese college students: A randomized controlled study protocol examining glycolipid and vascular endothelial responses
- Empagliflozin attenuates ISO-induced myocardial injury through PGC-1α-mediated mitochondrial biogenesis and improved fatty acid metabolism
- School-based high-intensity interval training for children: a focused systematic review of implementation and school-relevant outcomes
- Moderate-intensity exercise versus high-intensity interval training to determine the optimal training intensity for walking rehabilitation in chronic stroke (HIT-Stroke Trial 2): a study protocol for a randomized controlled trial
BibTeX
@article{bischof2026mitochondrial,
title = {{Mitochondrial Biogenesis in Human Skeletal Muscle: High-Intensity Interval Training Versus Moderate-Intensity Continuous Training}},
author = {Kevin Bischof},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219537},
url = {https://www.mdpi.com/1422-0067/27/21/9537},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mitochondrial Biogenesis in Human Skeletal Muscle: High-Intensity Interval Training Versus Moderate-Intensity Continuous Training
AU - Kevin Bischof
PY - 2026
DA - 2026/10/25
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219537
UR - https://www.mdpi.com/1422-0067/27/21/9537
AB - Mitochondrial biogenesis is a hallmark adaptation to endurance exercise with broad implications for metabolic health and athletic performance. High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) both stimulate mitochondrial remodeling in human skeletal muscle, yet whether exercise intensity or total work performed is the principal determinant remains contested. This mini review synthesizes current evidence on the intensity-dependent activation of AMP-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)—a central transcriptional coactivator in mitochondrial biogenesis. The author critically examines the distinction between mitochondrial content and respiratory function, discusses how study design—particularly work-matched versus time-matched protocols—shapes comparative conclusions, and identifies key unresolved questions including sex-based differences, fiber-type specificity, and the role of mitochondrial dynamics. The evidence indicates that both modalities are effective but operate through overlapping yet intensity-sensitive mechanisms; the metabolic-stress hypothesis provides a testable explanatory framework. Practical implications for exercise prescription are discussed. The review further considers the coordination of mitochondrial translation and turnover, mitochondrial Ca2+ handling, sex-specific evidence limitations, and translational outcomes in cardiometabolic disease.
SN - 1422-0067
ER -