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Annual Review of Physiology

Volume 87, 2025

Exercise as Mitochondrial Medicine: How Does the Exercise Prescription Affect Mitochondrial Adaptations to Training?

  • David J. Bishop1, Matthew J.-C. Lee1,2 and Martin Picard3,4,5,6
  • 1The Exercise Prescription Lab, The Institute for Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia; email: [email protected] 2Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia 3Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, Columbia University, New York, NY, USA 4Department of Neurology, H. Houston Merritt Center for Neuromuscular and Mitochondrial Diseases, Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center, Columbia University, New York, NY, USA 5New York State Psychiatric Institute, New York, NY, USA 6Robert N. Butler Columbia Aging Center, Columbia University Mailman School of Public Health, Columbia University, New York, NY, USA
  • Vol. 87:107-129 (Volume publication date February 2025)
  • First published as a Review in Advance on December 10, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Mitochondria are multifaceted organelles with several life-sustaining functions beyond energy transformation, including cell signaling, calcium homeostasis, hormone synthesis, programmed cell death (apoptosis), and others. A defining aspect of these dynamic organelles is their remarkable plasticity, which allows them to sense, respond, and adapt to various stressors. In particular, it is well-established that the stress of exercise provides a powerful stimulus that can trigger transient or enduring changes to mitochondrial molecular features, activities, integrated functions, behaviors, and cell-dependent mitochondrial phenotypes. Evidence documenting the many beneficial mitochondrial adaptations to exercise has led to the notion of exercise as a mitochondrial medicine. However, as with other medicines, it is important to understand the optimal prescription (i.e., type, dose, frequency, duration). In this review, we build on a systematic biological framework that distinguishes between domains of mitochondrial biology to critically evaluate how different exercise prescription variables influence mitochondrial adaptations to training.

Keyword(s): cardiorespiratory, cristae, dynamics, mitochondrial content, oxidative phosphorylation, resistance, respiration
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/content/journals/10.1146/annurev-physiol-022724-104836
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Exercise as Mitochondrial Medicine: How Does the Exercise Prescription Affect Mitochondrial Adaptations to Training?
Annual Review of Physiology 87, 107 (2025); https://doi.org/10.1146/annurev-physiol-022724-104836
/content/journals/10.1146/annurev-physiol-022724-104836
/content/journals/10.1146/annurev-physiol-022724-104836
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