Molecular basis of exercise-induced skeletal muscle mitochondrial biogenesis: historical advances, current knowledge, and future challenges
Open accessAbstract
We provide an overview of groundbreaking studies that laid the foundation for our current understanding of exercise-induced mitochondrial biogenesis and its contribution to human skeletal muscle fitness. We highlight the mechanisms by which skeletal muscle responds to the acute perturbations in cellular energy homeostasis evoked by a single bout of endurance-based exercise and the adaptations resulting from the repeated demands of exercise training that ultimately promote mitochondrial biogenesis through hormetic feedback loops. Despite intense research efforts to elucidate the cellular mechanisms underpinning mitochondrial biogenesis in skeletal muscle, translating this basic knowledge into improved metabolic health at the population level remains a future challenge.
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Several proteins needed for mitochondrial biogenesis are encoded in nuclear DNA and synthesized by cytosolic ribosomes before they can be imported into the mitochondria.
“Moreover, several proteins needed for mitochondrial biogenesis are encoded in nuclear DNA and synthesized by cytosolic ribosomes before they can be imported into the mitochondria (Jornayvaz and Shulman, 2010; Perry and Hawley, 2018).”
From Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities (2021) · cites this paper as Perry and Hawley, 2018
In “The Dawn of Molecular Biology” (page not provided), the paper says nuclear genes encode mitochondrial proteins and gives TFAM as a nuclear-encoded protein that accumulates in mitochondria. It does not specify that these proteins are synthesized by cytosolic ribosomes before import, so that part of the claim is not supported by our copy. (LLM, conf=0.83)
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- Authors
- Perry, C. G. R., & Hawley, J. A.
- Affiliations
- York University (CA)
- Liverpool John Moores University (GB)
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-05-15
- Volume
- 8
- Issue
- 9
- Pages
- a029686
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC6120690
- OpenAlex
- W2614244751
- Cited by
- 130
- References
- 24
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 10 · 2023: 6 · 2022: 12 · 2021: 37 · 2020: 25 · 2019: 15 · 2018: 3 · 2017: 3 · 2015: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Liverpool John Moores University (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Funders
- Novo Nordisk
- Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- Novo Nordisk Fonden (NNF14OC0011493)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitochondrial biogenesis, skeletal muscle, exercise training, endurance exercise, energy homeostasis, hormesis, metabolic health, muscular fitness
- MeSH terms
- Adaptation, Physiological, Animals, Organelle Biogenesis, Health Promotion, Humans, Physical Conditioning, Animal, Signal Transduction, Exercise, Gene Expression, Muscle, Skeletal, Translational Research, Biomedical
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