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It remains unclear whether high-intensity interval exercise (HIIE) elicits distinct molecular responses to traditional endurance exercise relative to the total work performed. We aimed to investigate the influence of exercise intensity on acute perturbations to skeletal muscle mitochondrial function (respiration and reactive oxygen species) and metabolic and redox signaling responses. In a randomized, repeated measures crossover design, eight recreationally active individuals (24 ± 5 yr; V̇o 2peak : 48 ± 11 ml·kg −1 ·min −1 ) undertook continuous moderate-intensity [CMIE: 30 min, 50% peak power output (PPO)], high-intensity interval (HIIE: 5 × 4 min, 75% PPO, work matched to CMIE), and low-volume sprint interval (SIE: 4 × 30 s) exercise, ≥7 days apart. Each session included muscle biopsies at baseline, immediately, and 3 h postexercise for high-resolution mitochondrial respirometry ( Jo 2 ) and H 2 O 2  emission ( Jh 2 o 2 ) and gene and protein expression analysis. Immediately postexercise and irrespective of protocol, Jo 2  increased during complex I + II leak/state 4 respiration but Jh 2 o 2  decreased ( P &lt; 0.05). AMP-activated protein kinase and acetyl co-A carboxylase phosphorylation increased ~1.5 and 2.5-fold respectively, while thioredoxin-reductase-1 protein abundance was ~35% lower after CMIE vs. SIE ( P &lt; 0.05). At 3 h postexercise, regardless of protocol, Jo 2  was lower during both ADP-stimulated state 3 OXPHOS and uncoupled respiration ( P &lt; 0.05) but Jh 2 o 2  trended higher ( P &lt; 0.08) and PPARGC1A mRNA increased ~13-fold, and peroxiredoxin-1 protein decreased ~35%. In conclusion, intermittent exercise performed at high intensities has similar dynamic effects on muscle mitochondrial function compared with endurance exercise, irrespective of whether total workload is matched. This suggests exercise prescription can accommodate individual preferences while generating comparable molecular signals known to promote beneficial metabolic adaptations.

american journal of physiology. regulatory, integrative and comparative physiology/american journal of physiology. regulatory, integrative, and comparative physiology

Acute HIIE elicits similar changes in human skeletal muscle mitochondrial H<sub>2</sub>O<sub>2</sub> release, respiration, and cell signaling as endurance exercise even with less work

Acute HIIE elicits similar changes in human skeletal muscle mitochondrial H2O2 release, respiration, and cell signaling as endurance exercise even with less work

Acute HIIE elicits similar changes in human skeletal muscle mitochondrial H₂O₂ release, respiration, and cell signaling as endurance exercise even with less work