Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27153-3
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Funding
- ANZ-MASON Foundation
- Australian Research Council [DP140104165]
- Australian National Health and Medical Research Council (NHMRC) [1140906, 1140851, 1155244]
- JDRF Australia (JDRF Career Development)
- Victorian Government's Operational Infrastructure Support Program
- National Health and Medical Research Council of Australia [1140906, 1155244] Funding Source: NHMRC
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Through the use of multiple omics techniques, the study uncovered a complex network of non-stoichiometric mitochondrial adaptations during different phases of exercise training. The findings suggest that enhancing electron flow to oxidative phosphorylation (OXPHOS) is more crucial for improving ATP generation than increasing the abundance of the OXPHOS machinery. The study challenges current understanding and calls for a careful reinterpretation of previous findings on training-induced mitochondrial adaptations.
Exercise training can be therapeutic but how mitochondria respond remains unclear. Here, the authors use multiple omics techniques to reveal a complex network of non-stoichiometric mitochondrial adaptations that are prioritized or deprioritised during different phases of exercise training. 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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