Complex I is bypassed during high intensity exercise
Journal article, 2019

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.

Author

Avlant Nilsson

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Elias Björnson

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Wallenberg Lab.

Mikael Flockhart

The Swedish School of Sport and Health Sciences (GIH)

Filip J. Larsen

The Swedish School of Sport and Health Sciences (GIH)

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Novo Nordisk Foundation Center for Biosustainability

Technical University of Denmark (DTU)

Nature Communications

2041-1723 (ISSN)

Vol. 10 1 5072

Subject Categories

Pharmaceutical Sciences

Sport and Fitness Sciences

Physiology

DOI

10.1038/s41467-019-12934-8

PubMed

31699973

More information

Latest update

12/3/2019