Mitochondrial Biogenesis in Human Skeletal Muscle: High-Intensity Interval Training Versus Moderate-Intensity Continuous Training

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.