The mitochondrial multi-omic response to exercise training across tissues

Abstract

Mitochondria are adaptable organelles with diverse cellular functions critical to whole-body metabolic homeostasis. While chronic endurance exercise training is known to alter mitochondrial activity, these adaptations have not yet been systematically characterized. Here, 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. We identified exercise upregulated networks that are downregulated in human type 2 diabetes and liver cirrhosis. In both cases HSD17B10, a central dehydrogenase in multiple metabolic pathways and mitochondrial tRNA maturation, was the main hub. In summary, we provide a multi-omic, cross-tissue atlas of the mitochondrial response to training and identify candidates for prevention of disease-associated mitochondrial dysfunction.

Mitochondrial Genome Variation in Polish Elite Athletes

“…Nilsson and Tarnopolsky (2019) have suggested that in the general population, aerobic exercise training of older adults may partially reverse mitochondrial dysfunction by increasing the mtDNA copy number and mitochondrial volume, transcript and protein expression, and OXPHOS efficiency [ 33 ]. One should note, however, that chronic training is a stressor that results in improvements in mitochondrial volume, structure, and functioning only in organs/tissues experiencing an increased energy demand [ 34 ].…”

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

“…Quantification of mitochondrial DNA (mtDNA) was performed and described by Amar, et al . 115 . Briefly, real-time quantitative PCR was performed in duplicate for each of the scWAT samples selected for -omics analysis.…”

Impact of genome build on RNA-seq interpretation and diagnostics

“…An additional 128 samples were processed with the Universal Plus™ mRNA-Seq with NuQuant library prep protocol from Tecan, which includes globin and ribosomal RNA depletion following the same protocol as Amar et al 59 . These samples were processed in an automated protocol on a Biomek i7 robotic liquid handling system.…”