Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle
Open accessAbstract
Mitochondrial dysfunction is a hallmark of multiple metabolic complications. Physical activity is known to increase mitochondrial content in skeletal muscle, counteracting age-related decline in muscle function and protecting against metabolic and cardiovascular complications. Here, we investigated the effect of 4 months of exercise training on skeletal muscle mitochondria electron transport chain complexes and supercomplexes in 26 healthy, sedentary older adults. Exercise differentially modulated respiratory complexes. Complex I was the most upregulated complex and not stoichiometrically associated to the other complexes. In contrast to the other complexes, complex I was almost exclusively found assembled in supercomplexes in muscle mitochondria. Overall, supercomplex content was increased after exercise. In particular, complexes I, III, and IV were redistributed to supercomplexes in the form of I+III 2+IV. Taken together, our results provide the first evidence that exercise affects the stoichiometry of supercomplex formation in humans and thus reveal a novel adaptive mechanism for increased energy demand.
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Endurance exercise increases the activity of muscle oxidative enzymes and FAO, in part from increased volume of the mitochondrial reticulum and elevated levels of cardiolipin, a lipid necessary for the assembly of OXPHOS complexes.
“Endurance exercise increases the activity of muscle oxidative enzymes and FAO, in part from increased volume of the mitochondrial reticulum and elevated levels of cardiolipin, a lipid that is necessary for the assembly of OXPHOS complexes (41, 51, 225).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [225]
Physical activity has established benefits on mitochondrial efficiency in aged skeletal muscle.
“The established benefits of physical activity on mitochondrial efficiency in aged skeletal muscle2,47,59”
From Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities (2019) · cites this paper as [47]
Mitochondria electron transport chain supercomplex assembly is promoted by exercise and results in increased maximal O2 consumption and mitochondrial respiratory capacity as well as increased reliance on fatty acid oxidation during exercise.
“Instead, mitochondria electron transport chain supercomplex assembly is promoted by exercise (Figure 3) and resulted in increased maximal O2 consumption and mitochondrial respiratory capacity as well as increased reliance on fatty acid oxidation during exercise (Greggio et al., 2017).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Greggio et al., 2017
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Self-citation
- Authors
- Greggio, C., Jha, P., Kulkarni, S. S., Lagarrigue, S., Broskey, N. T., Boutant, M., Wang, X., Conde Alonso, S., Ofori, E., Auwerx, J., Cantó, C., & Amati, F.
- Affiliations
- University of Lausanne (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Auwerx, Johan
- Cantó, Carles
- Amati, Francesca
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 25
- Issue
- 2
- Pages
- 301-311
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2558143992
- Cited by
- 286
- References
- 52
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 34 · 2023: 26 · 2022: 28 · 2021: 42 · 2020: 36 · 2019: 27 · 2018: 29 · 2017: 12
- FWCI
- 11.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion, cc-by-nc)
- SERVAL (Université de Lausanne) (submittedVersion, cc-by-nc)
- Funders
- Swiss National Science Foundation (SNSF) (PZ00P3-126339, PZ00P3-149398, 320030_170062)
- Leenaards Foundation
- BASPO
- EPFL
- NIH (R01AG043930)
- Systems X (SySX.ch 2013/153)
- SNSF (31003A-140780)
- EU Marie Skłodowska-Curie ITN (H2020-MSCA-ITN-2015-ChroMe - 675610)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- respiratory chain supercomplexes, exercise training, skeletal muscle mitochondria, respiratory chain complexes, complex I, cytochrome bc1 complex, cytochrome c oxidase, mitochondrial biogenesis, mitochondrial dysfunction, older adults, energy demand
- MeSH terms
- Aged, Aging, Female, Humans, Male, Middle Aged, Oxygen, Exercise, Muscle, Skeletal, Cell Respiration, Electron Transport Chain Complex Proteins, Adiposity
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