Cited by 93Mitochondrial Function and PathologyAdipose Tissue and MetabolismCardiovascular and exercise physiology

High-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content

Open access
Granata, Cesare, Caruana, Nikeisha J., Botella, Javier, Jamnick, Nicholas A., Huynh, Kevin, Kuang, Jujiao, Janssen, Hans A., Reljic, Boris +9 more·2021·Nature Communications

Published version of a preprint

Abstract

Mitochondrial defects are implicated in multiple diseases and aging. Exercise training is an accessible, inexpensive therapeutic intervention that can improve mitochondrial bioenergetics and quality of life. By combining multiple omics techniques with biochemical and in silico normalisation, we removed the bias arising from the training-induced increase in mitochondrial content to unearth an intricate and previously undemonstrated network of differentially prioritised mitochondrial adaptations. We show that changes in hundreds of transcripts, proteins, and lipids are not stoichiometrically linked to the overall increase in mitochondrial content. Our findings suggest enhancing electron flow to oxidative phosphorylation (OXPHOS) is more important to improve ATP generation than increasing the abundance of the OXPHOS machinery, and do not support the hypothesis that training-induced supercomplex formation enhances mitochondrial bioenergetics. Our study provides an analytical approach allowing unbiased and in-depth investigations of training-induced mitochondrial adaptations, challenging our current understanding, and calling for careful reinterpretation of previous findings.

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  1. [13]Pesta, D. & Gnaiger, E. in Mitochondrial Bioenergetics: Methods and Protocols 810 (eds Carlos M. Palmeira & Antonio J. Moreno) 25–58 (Springer Science+Business Media, 2012).
  2. [24]Morgan, T., Cobb, L., Short, F., Ross, R. & Gunn, D. in Muscle Metabolism During Exercise p. 87–95 (Springer, 1971).

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Authors
Granata, C., Caruana, N. J., Botella, J., Jamnick, N. A., Huynh, K., Kuang, J., Janssen, H. A., Reljic, B., Mellett, N. A., Laskowski, A., Stait, T. L., Frazier, A. E., Coughlan, M. T., Meikle, P. J., Thorburn, D. R., Stroud, D. A., & Bishop, D. J.
Affiliations
  • Deutsches Diabetes-Zentrum e.V. (DE)
  • The University of Melbourne (AU)
  • Victoria University (AU)
  • Deakin University (AU)
  • Baker Heart and Diabetes Institute (AU)
  • Monash University (AU)
  • Royal Children's Hospital (AU)
Corresponding author
  • Granata, Cesare
  • Stroud, David A.
  • Bishop, David J.
Venue
Nature Communications
Published
2021-12-03
Volume
12
Issue
1
Pages
7056-7056
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3215897669
Cited by
93
References
100
Citations by year
2026: 10 · 2025: 22 · 2024: 19 · 2023: 22 · 2022: 20
FWCI
4.86
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Victoria University Research Repository (Victoria University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Own your potential (DEAKIN) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
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 › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
high-intensity training, mitochondrial proteome, skeletal muscle, mitochondrial content, electron transport chain, oxidative phosphorylation, supercomplex formation, mitochondrial bioenergetics, exercise adaptation, mitochondrial lipid metabolism, transcriptome, proteome, multi-omics integration
MeSH terms
High-Intensity Interval Training, Adaptation, Physiological, Adenosine Triphosphate, Adolescent, Adult, Biopsy, Electron Transport, Energy Metabolism, Humans, Male, Mitochondria, Oxidative Phosphorylation, Quality of Life, Muscle, Skeletal, Proteome, Young Adult, Healthy Volunteers

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