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Stochastic mitochondrial DNA changes: bioenergy decline in type I skeletal muscle fibres correlates with a decline in the amount of amplifiable full-length mtDNA

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Abstract

Extra-long PCR (XL-PCR) was used to assess the relative concentration of functional full-length mitochondrial DNA (mtDNA) in single type I human vastus lateralis muscle fibres of defined cytochrome c oxidase (COX)activity. Type I muscle fibres rely more on mitochondrial oxidative phosphorylation for their energy demands, compared to the other common fibre types (IIa, IIab and IIb) that principally depend on glycolysis for their energy requirements. A total of 60 single type I fibres were analyzed from 15 individuals (8males and 7 females) of various ages. COX positive muscle fibres were shown to contain amplifiable full-length mtDNA together with a small number of mtDNA rearrangements. By contrast, COX negative fibres did not contain detectable full-length mtDNA, but did contain aheterogeneous mixture of rearranged mtDNA species with the frequency and occurrence of each deletion varying considerably from fibre to fibre. These data lead us to the conclusion that the level of COX activity in type I muscle fibres is reflected by the amount of amplifiable full-length mtDNA. It is proposed that the amount of amplifiable full-length mtDNA constitutes the functional fraction of the total mtDNA. A comprehensive hypothesis that relates the dynamics of mtDNA turnover, mtDNA mutations, mtDNA damage and repair to the ageing process is discussed.

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Authors and Affiliations

  1. Centre for Molecular Biology and Medicine, Epworth Medical Centre, 185–187 Hoddle Street, Richmond, VIC, 3121, Australia

    George Kopsidas, Chunfang Zhang, Natalia Yarovaya, Sergey Kovalenko & Anthony W. Linnane

  2. Orthopaedic Department, Royal Melbourne Hospital, Gratten Street, Parkville, Richmond, VIC, 3052, Australia

    Stephen Graves

  3. Epworth Medical Centre, 173 Lennox Street, Richmond, VIC, 3121, Australia

    Martin Richardson

Authors
  1. George Kopsidas
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  2. Chunfang Zhang
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  3. Natalia Yarovaya
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  4. Sergey Kovalenko
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  5. Stephen Graves
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  6. Martin Richardson
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  7. Anthony W. Linnane
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Correspondence to Anthony W. Linnane.

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Kopsidas, G., Zhang, C., Yarovaya, N. et al. Stochastic mitochondrial DNA changes: bioenergy decline in type I skeletal muscle fibres correlates with a decline in the amount of amplifiable full-length mtDNA. Biogerontology 3, 29–36 (2002). https://doi.org/10.1023/A:1015290810222

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