Given the pivotal role of mitochondria in providing the energy required for activities of daily life, it is not surprising that mitochondrial adaptations have been associated with endurance performance and many age-related degenerative or metabolic diseases. These findings highlight the importance of a better understanding of how mitochondria change with physical activity, inactivity, and aging. Powerful mass spectrometry (MS)-based technologies are starting to be used by exercise scientists to provide unprecedented insights into how individual mitochondrial proteins change in response to different conditions. Both physical inactivity and aging have potent effects on hundreds of mitochondrial proteins, and these appear to be fibre-type-specific, as will be highlighted by the pioneering bed-rest and aging studies of Dr Marta Murgia (Germany/Italy). Dr Malene Lindholm (USA/Sweden) will then present some of the latest findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC), which describe the mitochondrial multi-omic response to exercise training across various tissues. Prof. David Bishop (Australia) will round out the discussion by describing the results of a meta-analysis and unpublished findings that provide exciting new insights into how mitochondria adapt to exercise. This topic will be of interest to the many delegates interested in athletic performance, as well as those interested in population health.
ECSS Paris 2023: IS-PN09
In the absence of sufficient mechanical loading, skeletal muscle undergoes atrophy with loss of strength and detrimental metabolic effects. This can occur due to physical inactivity (including bed rest), space flight, and aging, and may affect different muscle fibre types unequally. This presentation will highlight the findings from studies that have used mass spectrometry-based proteomics to compare single skeletal muscle fibres of healthy volunteers before and after 10 days of continuous bed rest (and 6 months of space flight), and also single skeletal muscle fibres from younger and older humans. Protein complexes responsible for force transmission and energy production by the mitochondria are strongly downregulated in the unloading phase, with different changes in slow (type I) and fast (type II) fibre types. Parallel proteomic analysis of muscle biopsies of astronauts before and after a 6-month mission on the International Space Station highlights similar changes caused by lack of gravity despite daily exercise. Similarly, human aging is characterised by diverging metabolic and protein quality control adaptations in the different fibre types. Whereas mitochondrial content declines with aging in both fiber types, glycolysis and glycogen metabolism are upregulated in slow but downregulated in fast muscle fibers. These changes in metabolism and sarcomere quality control may be related to the ability of slow, but not fast, muscle fibres to maintain their mass during aging. These single muscle fibre analyses by proteomics have elucidated mitochondrial alterations in a sub-type-specific manner, and lay a molecular basis for countermeasures to combat detrimental mitochondrial changes with inactivity and aging.
Read CV Marta MurgiaECSS Paris 2023: IS-PN09
Mitochondria are adaptable organelles with diverse cellular functions critical to whole-body metabolic homeostasis. While endurance exercise training is known to alter mitochondrial activity, these adaptations have not yet been systematically characterised. In this presentation, Dr Malene Lindholm will summarise recent findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC), mapped the longitudinal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats endurance trained for 1, 2, 4 or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart and skeletal muscle, while we detected mild responses in the brain, lung, small intestine and testes. The colon response was characterized by non-linear dynamics that resulted in upregulation of mitochondrial function that was more prominent in females. Brown adipose and adrenal tissues were characterized by substantial downregulation of mitochondrial pathways. Training induced a previously unrecognized robust upregulation of mitochondrial protein abundance and acetylation in the liver, and a concomitant shift in lipid metabolism. The striated muscles demonstrated a highly coordinated response to increase oxidative capacity, with the majority of changes occurring in protein abundance and post-translational modifications. This work has also revealed exercise upregulated networks that are downregulated in human type 2 diabetes and liver cirrhosis. This presentation will also provide delegates with a multi-omic, cross-tissue atlas of the mitochondrial response to training and identify candidates for prevention of disease-associated mitochondrial dysfunction.
Read CV Malene LindholmECSS Paris 2023: IS-PN09
Given the importance of mitochondrial biogenesis for skeletal muscle performance, considerable attention has been given to understanding the molecular changes that help to determine mitochondrial adaptations to exercise. With the adoption of high-throughput proteomics within the field, the depth of mitochondrial proteome coverage has increased many-fold within the last decade. Information on protein abundance changes following exercise training now exists for hundreds of mitochondrial proteins across multiple studies. In this session, Prof. Bishop will present unpublished ’omics data, and an unpublished meta-analysis of all mitochondrial proteomics studies to date, that provide new and exciting insights into the many molecular changes that contribute to exercise-induced mitochondrial adaptations. The results of training studies incorporating whole-muscle proteomics will then be used to highlight an intricate and previously undemonstrated network of differentially prioritised mitochondrial adaptations that occur in response to different types of training. It will be shown that changes in hundreds of transcripts, proteins, and lipids are not stoichiometrically linked to the overall increase in mitochondrial content. The results of single-fibre proteomics show how exercise intensity influences fibre recruitment and ultimately induces fibre-specific changes in mitochondrial proteins that can help to explain how different types of exercise induce divergent mitochondrial adaptations. Finally, this presentation will highlight how these exciting new tools can help exercise and sport scientists to better understand how best to prescribe exercise to achieve specific mitochondrial adaptations. The target audience will be both exercise and sport scientists with an interest in the mechanisms that underlie adaptations to exercise training.
Read CV David BishopECSS Paris 2023: IS-PN09