The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Gene shifting: a novel therapy for mitochondrial myopathy
Abstract
Mutations in mitochondrial DNA (mtDNA) are the most frequent causes of mitochondrial myopathy in adults. In the majority of cases mutant and wild-type mtDNAs coexist, a condition referred to as mtDNA heteroplasmy; however, the relative frequency of each species varies widely in different cells and tissues. Nearly complete segregation of mutant and wild-type mtDNAs has been observed in the skeletal muscle of many patients. In such patients mutant mtDNAs pre-dominate in mature myofibers but are rare or undetectable in skeletal muscle satellite cells cultured in vitro. This pattern is thought to result from positive selection for the mutant mtDNA in post-mitotic myofibers and loss of the mutant by genetic drift in satellite cells. Satellite cells are dormant myoblasts that can be stimulated to re-enter the cell cycle and fuse with existing myofibers in response to signals for muscle growth or repair. We tested whether we could normalize the mtDNA genotype in mature myofibers in a patient with mitochondrial myopathy by enhancing the incorporation of satellite cells through regeneration following injury or muscle hypertrophy, induced by either eccentric or concentric resistance exercise training. We show a remarkable increase in the ratio of wild-type to mutant mtDNAs, in the proportion of muscle fibers with normal respiratory chain activity and in muscle fiber cross-sectional area after a short period of concentric exercise training. These data show that it is possible to reverse the molecular events that led to expression of metabolic myopathy and demonstrate the effectiveness of this form of 'gene shifting' therapy.
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“This activation is accomplished with either eccentric or concentric resistance exercise, as shown in a patient with the G12315A tRNAleu(CUN) point mutation, where resistance training significantly improved heteroplasmic ratios and increased the number of respiratory-competent fibers in muscle fibers (Taivassalo et al., 1999).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Taivassalo et al., 1999
Citations
Cites
Neural adaptation to resistance training
SALE, D. G. (1988) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-198810001-00009 · Cited by 1,421
Muscle function after exercise-induced muscle damage and rapid adaptation
CLARKSON, P. M., NOSAKA, K., & BRAUN, B. (1992) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199205000-00004 · Cited by 970 · cited 3×
“Although the CK response to exercise-induced injury shows large inter-subject variability (19), peak values after one bout of high force eccentric exercise of the elbow flexors generally range from 1000 to 10 000 U/l and values of 6000 U/l and higher have been reported 2 days post-exercise (19,20).”
BackgroundUltrastructural changes after concentric and eccentric contractions of human muscle
Newham, D. J., McPhail, G., Mills, K. R., & Edwards, R. H. T. (1983) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(83)90058-8 · Cited by 602
MOLECULAR GENETIC ASPECTS OF HUMAN MITOCHONDRIAL DISORDERS
Larsson, N.-G., & Clayton, D. A. (1995) · Annual Review of Genetics · doi:10.1146/annurev.ge.29.120195.001055 · Cited by 493
Mechanism of work-induced hypertrophy of skeletal muscle
GOLDBERG, A. L., ETLINGER, J. D., GOLDSPINK, D. F., & JABLECKI, C. (1975) · Medicine and Science in Sports and Exercise · doi:10.1249/00005768-197500730-00016 · Cited by 402
Satellite cell activity is required for hypertrophy of overloaded adult rat muscle
Rosenblatt, J. D., Yong, D., & Parry, D. J. (1994) · Muscle & Nerve · doi:10.1002/mus.880170607 · Cited by 356
Boulet, L., Karpati, G., & Shoubridge, E. A. (1992) · Europe PMC (PubMed Central) · Cited by 331
Macintyre, D. L., Reid, W., & Mckenzie, D. (1995) · Sports Medicine · doi:10.2165/00007256-199520010-00003 · Cited by 275
Exercise-induced satellite cell activation in growing and mature skeletal muscle
Darr, K. C., & Schultz, E. (1987) · Journal of Applied Physiology · doi:10.1152/jappl.1987.63.5.1816 · Cited by 268
STAUBLR, W. T. (1989) · Exercise and Sport Sciences Reviews · doi:10.1249/00003677-198900170-00008 · Cited by 251
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van Eijsden, R. G. E., Eijssen, L., Lindsey, P. J., van den Burg, C. M. M., de Wit, L. E. A., Rubio‐Gozalbo, M. E., de Die-Smulders, C. E. M., Ayoubi, T., Sluiter, W., de Coo, I. F. M., et al. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.057497 · Cited by 13
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Taylor, R. W., Wardell, T. M., Lightowlers, R. N., & Turnbull, D. M. (2000) · Neurological Sciences · doi:10.1007/s100720070002 · Cited by 13
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Oldfors, A., & Tulinius, M. (2007) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)86006-4 · Cited by 8
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Vissing, J., & van Engelen, B. G. M. (2012) · Neuromuscular Disorders · doi:10.1016/j.nmd.2012.08.005 · Cited by 7
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Testa, M., Navazio, F. M., & Neugebauer, J. M. (2005) · Current Sports Medicine Reports · doi:10.1097/01.csmr.0000306223.19714.7a · Cited by 6
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van Eijsden, R. G. E. (2008) · Research Publications (Maastricht University) · doi:10.26481/dis.20080522re
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Geffroy, G. (2017) · theses.fr (ABES) · doi:10.70675/a2ae3815zb7a8z4cbcz9a2dz22dbcd055adb
Martin, I., Flickinger, J., Rahaman, I., Sarna, T., Ballance, E., Ginelli, N., Peterson, J. T., Uryash, A., Adams, J. A., Xiao, R., et al. (2026) · BMC Medicine · doi:10.1186/s12916-026-04944-3
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Metadata
- Authors
- Taivassalo, T.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Corresponding author
- Taivassalo, T
- ORCID
- Taivassalo, T
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-06-01
- Volume
- 8
- Issue
- 6
- Pages
- 1047-1052
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2151218248
- Cited by
- 160
- References
- 25
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 8 · 2020: 2 · 2019: 8 · 2018: 2 · 2017: 2 · 2016: 9 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 6
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Muscular Dystrophy Association
- Killam Trusts
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- mitochondrial myopathy, mitochondrial heteroplasmy, mitochondrial DNA mutations, skeletal muscle satellite cells, myofiber regeneration, resistance training, concentric exercise, eccentric exercise, muscle fiber cross-sectional area, respiratory chain activity, metabolic myopathies, genetic drift
- MeSH terms
- Creatine Kinase, DNA, Mitochondrial, Exercise Therapy, Gene Expression Regulation, Genotype, Humans, Male, Middle Aged, Muscle Contraction, Mutation, Phenotype, RNA, Transfer, Leu, Mitochondrial Myopathies, Muscle, Skeletal
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