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- Title
Complex I is bypassed during high intensity exercise.
- Authors
Nilsson, Avlant; Björnson, Elias; Flockhart, Mikael; Larsen, Filip J.; Nielsen, Jens
- Abstract
Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise. During high-intensity exercise, muscles convert glucose to lactate, in a process that is energetically less efficient than respiration. Here the authors develop a computational model based on muscle proteomic data showing that bypassing mitochondrial complex I increases ATP production rates, and validate these model predictions in an exercise test on 5 subjects.
- Subjects
COMPLEX ions; MUSCLES; LACTATES; GLUCOSE; METABOLIC models
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-12934-8