ArticleNature communications2019
Complex I is bypassed during high intensity exercise.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Citius, Maius, Melius: Mitochondria and Endurance Performance.Sports medicine (Auckland, N.Z.) · 2026Review
- Reconstruction of human metabolic models with large language models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Reversing Mitochondrial Dysfunction in Optineurin E50K Glaucoma: A Metabolic Approach to Neuroprotection.Research square · 2026Article
- Intracerebroventricular infusion of exercise donor plasma exosomes induces molecular changes indicating exercise-like adaptations in basal ganglia cells of older male rats.Frontiers in aging neuroscience · 2026Article
- Modeling for understanding and engineering metabolism.QRB discovery · 2025Article
- Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth.Innovation (Cambridge (Mass.)) · 2024Article
- Brain energy metabolism is optimized to minimize the cost of enzyme synthesis and transport.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multi-omics reveals changed energy metabolism of liver and muscle by caffeine after mice swimming.PeerJ · 2024Article
- 5-Aminolevulinic acid bypasses mitochondrial complex I deficiency and corrects physiological dysfunctions in Drosophila.Human molecular genetics · 2023Article
- A Simple Model for Diagnosis of Maladaptations to Exercise Training.Sports medicine - open · 2022Article
- Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0.Nature communications · 2022Article
- Artificial neural networks enable genome-scale simulations of intracellular signaling.Nature communications · 2022Article
- Machine learning-guided evaluation of extraction and simulation methods for cancer patient-specific metabolic models.Computational and structural biotechnology journal · 2022Article
- Potential Role of Chronic Physical Exercise as a Treatment in the Development of Vitiligo.Frontiers in physiology · 2022Article
- Effects of Plyometric Training on Soft and Hard Surfaces for Improving Running Economy.Journal of human kinetics · 2021Article
- Re-Evaluating the Oxidative Phenotype: Can Endurance Exercise Save the Western World?Antioxidants (Basel, Switzerland) · 2021Review
- Contextualizing the biological relevance of standardized high-resolution respirometry to assess mitochondrial function in permeabilized human skeletal muscle.Acta physiologica (Oxford, England) · 2021Article
- Exercise Is Medicine…and the Dose Matters.Frontiers in physiology · 2021Article
- IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Uncoupling mitochondrial uncoupling from alternative substrate utilization: implications for heavy intensity exercise.The Journal of physiology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.