Training-induced bioenergetic improvement in human skeletal muscle is associated with non-stoichiometric changes in the mitochondrial proteome without reorganization of respiratory chain content

Mitochondrial defects are implicated in multiple diseases and aging. Exercise training is an accessible and inexpensive therapeutic intervention improving mitochondrial bioenergetics and quality of life. By combining a multi-omics approach with biochemical and in silico normalization, we removed the...

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Published inbioRxiv
Main Authors Granata, Cesare, Caruana, Nikeisha J, Botella, Javier, Jamnick, Nicholas A, Huynh, Kevin, Kuang, Jujiao, Janssen, Hans A, Reljic, Boris, Mellett, Natalie A, Laskowski, Adrienne, Stait, Tegan L, Frazier, Ann E, Coughlan, Melinda T, Meikle, Peter J, Thorburn, David R, Stroud, David Arthur, Bishop, David J
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 29.03.2021
Subjects
Adaptation
Aging
Bioenergetics
Electron transport
Lipids
Mitochondria
Musculoskeletal system
Oxidation
Oxidative phosphorylation
Phosphorylation
Physical training
Proteomes
Quality of life
Skeletal muscle
Tricarboxylic acid cycle
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Summary:Mitochondrial defects are implicated in multiple diseases and aging. Exercise training is an accessible and inexpensive therapeutic intervention improving mitochondrial bioenergetics and quality of life. By combining a multi-omics approach with biochemical and in silico normalization, we removed the bias arising from the training-induced increase in human skeletal muscle mitochondrial content to unearth an intricate and previously undemonstrated network of differentially prioritized mitochondrial adaptations. We show that changes in hundreds of transcripts, proteins, and lipids are not stoichiometrically linked to the increase in mitochondrial content. We demonstrate that enhancing electron flow to oxidative phosphorylation (OXPHOS) is more important to improve ATP generation than increasing the abundance of the OXPHOS machinery, and that training-induced supercomplex formation does not confer enhancements in mitochondrial bioenergetics. Our study provides a new 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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.02.19.431993