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Cited by 160Mitochondrial Function and PathologyMuscle Physiology and DisordersAmyotrophic Lateral Sclerosis Research

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

Taivassalo, T·1999·Human Molecular Genetics
DOI 10.1093/hmg/8.6.1047
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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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Crossref · 10.1093/hmg/8.6.1047

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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
DOI
10.1093/hmg/8.6.1047
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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