Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression.

Wright, David C.; Han, Dong-Ho; Garcia-Roves, Pablo M.; Geiger, Paige C.; Jones, Terry E.; Holloszy, John O.

doi:10.1074/jbc.m606116200

Cited by 488Adipose Tissue and MetabolismMitochondrial Function and PathologyMetabolism, Diabetes, and Cancer

Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression.

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Wright, David C., Han, Dong-Ho, Garcia-Roves, Pablo M., Geiger, Paige C., Jones, Terry E., Holloszy, John O.·2007·Journal of Biological Chemistry

DOI 10.1074/jbc.m606116200

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Abstract

Exercise results in rapid increases in expression of the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and in mitochondrial biogenesis in skeletal muscle. PGC-1alpha regulates and coordinates mitochondrial biogenesis, and overexpression of PGC-1alpha in muscle cells results in increases in mitochondrial content. In this context, it has been proposed that the increase in PGC-1alpha protein expression mediates the exercise-induced increase in mitochondrial biogenesis. However, we found that mitochondrial proteins with a short half-life increase as rapidly as, or more rapidly than, PGC-1alpha protein. This finding led us to hypothesize that activation, rather than increased expression, of PGC-1alpha mediates the initial phase of the exercise-induced increase in mitochondria. In this study, we found that most of the PGC-1alpha in resting skeletal muscle is in the cytosol. Exercise resulted in activation of p38 MAPK and movement of PGC-1alpha into the nucleus. In support of our hypothesis, binding of the transcription factor nuclear respiratory factor 1 (NRF-1) to the cytochrome c promoter and NRF-2 to the cytochrome oxidase subunit 4 promoter increased in response to exercise prior to an increase in PGC-1alpha protein. Furthermore, exercise-induced increases in the mRNAs of cytochrome c, delta-aminolevulinate synthase, and citrate synthase also occurred before an increase in PGC-1 protein. Thus, it appears that activation of PGC-1alpha may mediate the initial phase of the exercise-induced adaptive increase in muscle mitochondria, whereas the subsequent increase in PGC-1alpha protein sustains and enhances the increase in mitochondrial biogenesis.

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OXPHOS expression can be increased with exercise training, a potent insulin sensitizer.
“Conversely, OXPHOS expression can be increased with exercise training (133, 135), a potent insulin sensitizer.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [135]

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Authors: Wright, D. C., Han, D.-H., Garcia-Roves, P. M., Geiger, P. C., Jones, T. E., & Holloszy, J. O.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Holloszy, John O.
ORCID: Wright, David C.
Han, Dong-Ho
Geiger, Paige C.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2007-01
Volume: 282
Issue: 1
Pages: 194-199
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m606116200
OpenAlex: W2020893322
Cited by: 488
References: 38
Citations by year: 2026: 17 · 2025: 10 · 2024: 16 · 2023: 11 · 2022: 16 · 2021: 16 · 2020: 20 · 2019: 27 · 2018: 26 · 2017: 46 · 2016: 15 · 2015: 33 · 2014: 27 · 2013: 36 · 2012: 30
FWCI: 13.73
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5012 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
Funders: National Institute on Aging (AG00425, AG 00078)
National Institute of Diabetes and Digestive and Kidney Diseases (DK070425, F32DK070425, P30DK056341)
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: physical activity, mitochondrial biogenesis, PGC-1α, skeletal muscle, p38 MAPK, nuclear translocation, NRF1, Nrf2, cytochrome c, delta-aminolevulinic acid synthase, citrate synthase, exercise adaptation
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Cell Nucleus, Chromatin, Cytosol, Male, Mitochondria, Muscles, Promoter Regions, Genetic, RNA, Messenger, Transcription Factors, Blotting, Western, RNA-Binding Proteins, Rats, Wistar, DNA Primers, Muscle, Skeletal, Rats

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Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression.

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