The mitochondrial multi-omic response to exercise training across rat tissues.

Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart, and skeletal muscle. The colon showed non-linear response dynamics, whereas mitochondrial pathways were downregulated in brown adipose and adrenal tissues. Protein acetylation increased in the liver, with a shift in lipid metabolism, whereas oxidative proteins increased in striated muscles. Exercise-upregulated networks were downregulated in human diabetes and cirrhosis. Knockdown of the central network protein 17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) elevated oxygen consumption, indicative of metabolic stress. We provide a multi-omic, multi-tissue, temporal atlas of the mitochondrial response to exercise training and identify candidates linked to mitochondrial dysfunction. [Display omitted] • Multi-omic atlas of the mitochondrial response to exercise training in 19 rat tissues • Robust temporal differences in mitochondrial response by -omes, tissues, and sex • Most dynamic responses in adrenal, brown adipose, colon, heart, liver, and muscle • Protein networks upregulated by exercise are downregulated in human T2D and cirrhosis Amar et al. delineate the extensive molecular modifications occurring in mitochondria, central metabolic organelles, in response to endurance exercise training across diverse rat tissues. Their translational analysis suggests clinical relevance of the metabolic regulator HSD17B10. Its suppression induces metabolic stress in liver cells, underlining its potential role in disease pathology. [ABSTRACT FROM AUTHOR]