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

David Amar1, Nicole R Gay1, David Jimenez-Morales1

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Chronic endurance exercise significantly alters mitochondrial function across 19 tissues in rats. This study maps these adaptations, revealing exercise-induced changes that may protect against diseases like type 2 diabetes.

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Area of Science:

  • Mitochondrial biology
  • Exercise physiology
  • Systems biology

Background:

  • Mitochondria are vital for metabolic homeostasis, but exercise-induced adaptations remain poorly understood.
  • Systematic, multi-omic characterization of mitochondrial changes due to endurance training is needed.

Approach:

  • The Molecular Transducers of Physical Activity (MoTrPaC) Consortium conducted a longitudinal, multi-omic study.
  • 19 tissues from male and female rats were analyzed after 1, 2, 4, or 8 weeks of endurance training.
  • Analyzed mitochondrial analytes, protein abundance, and post-translational modifications.

Key Points:

  • Significant mitochondrial adaptations occurred in adrenal gland, brown adipose, colon, heart, and skeletal muscle.
  • Colon showed non-linear, female-predominant upregulation; brown adipose and adrenal showed downregulation.
  • Liver exhibited robust upregulation of mitochondrial protein and acetylation, shifting lipid metabolism.
  • Striated muscles increased oxidative capacity via coordinated protein and PTM changes.
  • Exercise-upregulated networks were found to be downregulated in human type 2 diabetes and liver cirrhosis, with HSD17B10 as a key hub.

Conclusions:

  • This study provides a comprehensive multi-omic atlas of mitochondrial responses to endurance training across tissues.
  • Identified exercise-responsive mitochondrial pathways and key molecules like HSD17B10.
  • Findings suggest potential therapeutic targets for preventing or treating diseases linked to mitochondrial dysfunction.