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

C Granata; NJ Caruana; J Botella; NA Jamnick; K Huynh; J Kuang; HA Janssen; B Reljic; NA Mellett; A Laskowski; TL Stait; AE Frazier; MT Coughlan; PJ Meikle; DR Thorburn; DA Stroud; DJ Bishop

Journal article

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

C Granata, NJ Caruana, J Botella, NA Jamnick, K Huynh, J Kuang, HA Janssen, B Reljic, NA Mellett, A Laskowski, TL Stait, AE Frazier, MT Coughlan, PJ Meikle, DR Thorburn, DA Stroud, DJ Bishop

Nature Communications | Published : 2021

DOI: 10.1038/s41467-021-27153-3

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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 t..

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University of Melbourne Researchers

Nikeisha Caruana Author

Ann Frazier Author

Peter Meikle Author

David Thorburn Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

We thank the participants for their time and commitment to this study. The authors would like to acknowledge all members of the Stroud and Bishop labs for input into interpretation and presentation of data. We thank the Bio21 Mass Spectrometry and Proteomics Facility (MMSPF) for provision of instrumentation, training and technical support. We acknowledge the use of the services and facilities of the Australian Genome Research Facility (AGRF). This study was funded by grants from the ANZ-MASON Foundation (to D.J.B), the Australian Research Council (Discovery Project DP140104165 to D.J.B), the Australian National Health and Medical Research Council (NHMRC Project Grant 1140906 to D.A.S.; NHMRC Fellowships 1140851 to D.A.S. and 1155244 to D.R.T.), JDRF Australia (JDRF Career Development to M.T.C.), and the Australian Research Council Special Research Initiative in Type 1 Juvenile Diabetes (to M.T.C.). We acknowledge the support of the Mito Foundation for the provision of instrumentation and the Victorian Government's Operational Infrastructure Support Program.