The mitochondrial multi-omic response to exercise training across rat tissues
David Amar, Nicole R. Gay, David Jimenez‐Morales, Pierre M. Jean Beltran, Megan E. Ramaker, Archana N. Raja, Bingqing Zhao, Yifei Sun, Shruti Marwaha, David A. Gaul, Steven G. Hershman, Alexis Ferrasse, Ashley Xia, Ian R. Lanza, Facundo M. Fernández, Stephen B. Montgomery, Andrea L. Hevener, Euan A. Ashley, Martin J. Walsh, Lauren M. Sparks, Charles Burant, R. Scott Rector, John P. Thyfault, Matthew T. Wheeler, Bret H. Goodpaster, Paul M. Coen, Simon Schenk, Sue C. Bodine, Maléne E. Lindholm, Joshua N. Adkins, Jose Juan Almagro Armenteros, Mary Anne S. Amper, Dam Bae, Marcas Bamman, Nasim Bararpour, Jerry Barnes, Bryan C. Bergman, Daniel H. Bessesen, Nicholas T. Broskey, Thomas W. Buford, Steven Carr, Toby L. Chambers, Clarisa Chavez, Roxanne Chiu, Natalie Clark, Gary Cutter, Charles R. Evans, Edziu Franczak, Nicole Gagne, Yongchao Ge, Krista M. Hennig, Joseph A. Houmard, Kim M. Huffman, Chia-Jui Hung, Chelsea Hutchinson-Bunch, Olga Ilkayeva, Bailey E. Jackson, Catherine M. Jankowski, Christopher A. Jin, Neil M. Johannsen, Daniel H. Katz, Hasmik Keshishian, Wendy M. Kohrt, Kyle S. Kramer, William E. Kraus, Bridget Lester, Jun Z. Li, Ana K. Lira, Adam Lowe, D.R. Mani, Gina M. Many, Sandy May, Edward L. Melanson, Samuel G. Moore, Kerrie L. Moreau, Nicolas Musi, Daniel Nachun, Venugopalan D. Nair, Christopher Newgard, German Nudelman, Paul D. Piehowski, Hanna Pincas, Wei-Jun Qian, Tuomo Rankinen, Blake B. Rasmussen, Eric Ravussin, Jessica L. Rooney, Scott Rushing, Mihir Samdarshi, James A. Sanford, Irene E. Schauer, Stuart C. Sealfon, Kevin S. Smith, Gregory R. Smith, Michael Snyder, Cynthia L. Stowe, Jennifer W. Talton, Christopher Teng, Anna Thalacker-Mercer, Russell Tracy
Abstract
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.