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

Cesare Granata (), Nikeisha J. Caruana, Javier Botella, Nicholas A. Jamnick, Kevin Huynh, Jujiao Kuang, Hans A. Janssen, Boris Reljic, Natalie A. Mellett, Adrienne Laskowski, Tegan L. Stait, Ann E. Frazier, Melinda T. Coughlan, Peter J. Meikle, David R. Thorburn, David A. Stroud () and David J. Bishop ()
Additional contact information
Cesare Granata: Victoria University
Nikeisha J. Caruana: Victoria University
Javier Botella: Victoria University
Nicholas A. Jamnick: Victoria University
Kevin Huynh: Baker Heart & Diabetes Institute
Jujiao Kuang: Victoria University
Hans A. Janssen: Victoria University
Boris Reljic: The University of Melbourne
Natalie A. Mellett: Baker Heart & Diabetes Institute
Adrienne Laskowski: Monash University
Tegan L. Stait: Royal Children’s Hospital
Ann E. Frazier: Royal Children’s Hospital
Melinda T. Coughlan: Monash University
Peter J. Meikle: Baker Heart & Diabetes Institute
David R. Thorburn: Royal Children’s Hospital
David A. Stroud: The University of Melbourne
David J. Bishop: Victoria University

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27153-3

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