Complex I is bypassed during high intensity exercise

Avlant Nilsson, Elias Björnson, Mikael Flockhart, Filip J. Larsen, Jens Nielsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.

Original languageEnglish
Article number5072
JournalNature Communications
Volume10
Issue number1
Number of pages11
ISSN2041-1723
DOIs
Publication statusPublished - 2019

Cite this

Nilsson, Avlant ; Björnson, Elias ; Flockhart, Mikael ; Larsen, Filip J. ; Nielsen, Jens. / Complex I is bypassed during high intensity exercise. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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Complex I is bypassed during high intensity exercise. / Nilsson, Avlant; Björnson, Elias; Flockhart, Mikael; Larsen, Filip J.; Nielsen, Jens.

In: Nature Communications, Vol. 10, No. 1, 5072, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

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AU - Larsen, Filip J.

AU - Nielsen, Jens

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Y1 - 2019

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